Memory B cell

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B lymphocytes are the cells of the immune system that make antibodies to invading pathogens like viruses. They form memory cells that remember the same pathogen for faster antibody production in future infections. Original antigenic sin.svg
B lymphocytes are the cells of the immune system that make antibodies to invading pathogens like viruses. They form memory cells that remember the same pathogen for faster antibody production in future infections.

In immunology, a memory B cell (MBC) is a type of B lymphocyte that forms part of the adaptive immune system. These cells develop within germinal centers of the secondary lymphoid organs. Memory B cells circulate in the blood stream in a quiescent state, sometimes for decades. [1] Their function is to memorize the characteristics of the antigen that activated their parent B cell during initial infection such that if the memory B cell later encounters the same antigen, it triggers an accelerated and robust secondary immune response. [2] [3] Memory B cells have B cell receptors (BCRs) on their cell membrane, identical to the one on their parent cell, that allow them to recognize antigen and mount a specific antibody response. [4]

Contents

Development and activation

T cell dependent mechanisms

In a T-cell dependent development pathway, naïve follicular B cells are activated by antigen-presenting follicular B helper T cells (TFH) during the initial infection, or primary immune response. [3] Naïve B cells circulate through follicles in secondary lymphoid organs (i.e. spleen and lymph nodes) where they can be activated by a floating foreign peptide brought in through the lymph or by antigen presented by antigen-presenting cells (APCs) such as dendritic cells (DCs). [5] B cells may also be activated by binding foreign antigen in the periphery where they then move into the secondary lymphoid organs. [3] A signal transduced by the binding of the peptide to the B cell causes the cells to migrate to the edge of the follicle bordering the T cell area. [5]

The B cells internalize the foreign peptides, break them down, and express them on class II major histocompatibility complexes (MHCII), which are cell surface proteins. Within the secondary lymphoid organs, most of the B cells will enter B-cell follicles where a germinal center will form. Most B cells will eventually differentiate into plasma cells or memory B cells within the germinal center. [3] [6] The TFHs that express T cell receptors (TCRs) cognate to the peptide (i.e. specific for the peptide-MHCII complex) at the border of the B cell follicle and T-cell zone will bind to the MHCII ligand. The T cells will then express the CD40 ligand (CD40L) molecule and will begin to secrete cytokines which cause the B cells to proliferate and to undergo class switch recombination, a mutation in the B cell's genetic coding that changes their immunoglobulin type. [7] [8] Class switching allows memory B cells to secrete different types of antibodies in future immune responses. [3] The B cells then either differentiate into plasma cells, germinal center B cells, or memory B cells depending on the expressed transcription factors. The activated B cells that expressed the transcription factor Bcl-6 will enter B-cell follicles and undergo germinal center reactions. [7]

Once inside the germinal center, the B cells undergo proliferation, followed by mutation of the genetic coding region of their BCR, a process known as somatic hypermutation. [3] The mutations will either increase or decrease the affinity of the surface receptor for a particular antigen, a progression called affinity maturation. After acquiring these mutations, the receptors on the surface of the B cells (B cell receptors) are tested within the germinal center for their affinity to the current antigen. [9] B cell clones with mutations that have increased the affinity of their surface receptors receive survival signals via interactions with their cognate TFH cells. [2] [3] [10] The B cells that do not have high enough affinity to receive these survival signals, as well as B cells that are potentially auto-reactive, will be selected against and die through apoptosis. [6] These processes increase variability at the antigen binding sites such that every newly generated B cell has a unique receptor. [11]

After differentiation, memory B cells relocate to the periphery of the body where they will be more likely to encounter antigen in the event of a future exposure. [6] [2] [3] Many of the circulating B cells become concentrated in areas of the body that have a high likelihood of coming into contact with antigen, such as the Peyer's patch.

The process of differentiation into memory B cells within the germinal center is not yet fully understood. [3] Some researchers hypothesize that differentiation into memory B cells occurs randomly. [6] [4] Other hypotheses propose that the transcription factor NF-κB and the cytokine IL-24 are involved in the process of differentiation into memory B cells. [11] [3] An additional hypothesis states that the B cells with relatively lower affinity for antigen will become memory B cells, in contrast to B cells with relatively higher affinity that will become plasma cells.

T cell independent mechanisms

Not all B cells present in the body have undergone somatic hypermutations. IgM+ memory B cells that have not undergone class switch recombination demonstrate that memory B cells can be produced independently of the germinal centers.

Primary response

Upon infection with a pathogen, many B cells will differentiate into the plasma cells, also called effector B cells, which produce a first wave of protective antibodies and help clear infection. [6] [2] Plasma cells secrete antibodies specific for the pathogens but they cannot respond upon secondary exposure. A fraction of the B cells with BCRs cognate to the antigen differentiate into memory B cells that survive long-term in the body. [12]  The memory B cells can maintain their BCR expression and will be able to respond quickly upon secondary exposure. [6]

Secondary response and memory

The memory B cells produced during the primary immune response are specific to the antigen involved during the first exposure. In a secondary response, the memory B cells specific to the antigen or similar antigens will respond. [3] When memory B cells reencounter their specific antigen, they proliferate and differentiate into plasma cells, which then respond to and clear the antigen. [3] The memory B cells that do not differentiate into plasma cells at this point can reenter the germinal centers to undergo further class switching or somatic hypermutation for further affinity maturation. [3] Differentiation of memory B cells into plasma cells is far faster than differentiation by naïve B cells, which allows memory B cells to produce a more efficient secondary immune response. [4] The efficiency and accumulation of the memory B cell response is the foundation for vaccines and booster shots. [4] [3]

The phenotype of memory cells that prognosticate plasma cells or germinal center cells fate has been discovered  few years ago. Based on expression microarray comparisons between memory B cells and naïve B cells, it was identified that there are several surface proteins, such as CD80, PD-L2 and CD73 that are only expressed on the memory B cells, so they also serve to divide this cells in multiple phenotypic subsets. [13] Moreover, it has been shown that the memory cells that express CD80, PD-L2 and CD73 are more likely to become plasma cells. On the other hand, the cells which don´t have these type of markers are more likely to form germinal center cells. The IgM+  memory B cells do not express CD80 or CD73, whereas IgG+ express them. Moreover, IgG+ are more likely to differenciate into antibody-secreting cells. [14]

Lifespan

Memory B cells can survive for decades, which gives them the capacity to respond to multiple exposures to the same antigen. [3] The long-lasting survival is hypothesized to be a result of certain anti-apoptosis genes that are more highly expressed in memory B cells than other subsets of B cells. [6] Additionally, the memory B cell does not need to have continual interaction with the antigen nor with T cells in order to survive long-term. [4]

However, it is true that the lifespan of individual memory B cells remains poorly defined, although they have a critical role in long-term immunity. In one study using a B cell receptor (BCR) transgenic system (it was a H chain transgenic mouse model which lacked secreted Ig, so it didn´t deposit Ag-containing immune complexes), it was shown that the number of memory B cells remain constant for a period of around 8–20 weeks after the immunization. It was also estimated that the half-life of memory B cells was between 8–10 weeks, after doing an experiment in which the cells were treated in vivo with bromodeoxyuridine. [15] In other experiments in mouse, it has been shown that the lifespan of memory B cells is at least 9 times greater than the lifespan of a follicular naïve B cell. [16]

Markers

Memory B cells are typically distinguished by the cell surface marker CD27, although some subsets do not express CD27. Memory B cells that lack CD27 are generally associated with exhausted B cells or certain autoimmune conditions such as HIV, lupus, or rheumatoid arthritis. [2] [3]

Because B cells have typically undergone class switching, they can express a range of immunoglobulin molecules. Some specific attributes of particular immunoglobulin molecules are described below:  

It is important to mention the importance of integration of signalling pathways related to the receptors of BCRs and TLRs in order to modulate the production of the antibodies by the expansion of the memory B cells. Therefore, there are different factors that provide the information in order to secret different types of antibodies. It has been demonstrated that the production of specific-IgG1, anaphylactic-IgG1 and total-IgE depends on the signal produce by TLR2 and Myd88. Moreover, the signal produce by TLR4 when it is stimulated by natterins (protein obtained from T. nattereri fish venom) accelerates the synthesis of the antibody IgE acting as an adjuvant, as it was shown in an in vivo experiment with mice. [17]

The receptor CCR6 is generally a marker of B cells that will eventually differentiate into MBCs. This receptor detects chemokines, which are chemical messengers that allow the B cell to move within the body. Memory B cells may have this receptor to allow them to move out of the germinal center and into the tissues where they have a higher probability of encountering antigen. [6]

It has been shown that memory B cells have high level expression of CCR6 as well as an increased chemotactic response to the CCR6 ligand (CCL20) in comparison with naïve B cells. Nevertheless, the primary humoral response and the maintenance of the memory B cells are not affected in CCR6-deficient mice. However, there is not an effective secondary response  from the memory B cells when there is a reexposure of the antigen if the cells do not express CCR6. Therefore we can confirm that CCR6 is essential for the ability of memory B cells to be recalled to their cognate antigen as well as for the appropriate anatomical positioning of these cells. [18]

Subsets

Germinal center independent memory B cells

This subset of cells differentiates from activated B cells into memory B cells before entering the germinal center. B cells that have a high level of interaction with TFH within the B cell follicle have a higher propensity of entering the germinal center. The B cells that develop into memory B cells independently from germinal centers likely experience CD40 and cytokine signaling from T cells. [4] Class switching can still occur prior to interaction with the germinal center, while somatic hypermutation only occurs after interaction with the germinal center. [4] The lack of somatic hypermutation is hypothesized to be beneficial; a lower level of affinity maturation means that these memory B cells are less specialized to a specific antigen and may be able to recognize a wider range of antigens. [11] [19] [4]

T-independent memory B cells

T-independent memory B cells are a subset called B1 cells. These cells generally reside in the peritoneal cavity. When reintroduced to antigen, some of these B1 cells can differentiate into memory B cells without interacting with a T cell. [4] These B cells produce IgM antibodies to help clear infection. [20]

T-bet memory B cells

T-bet B cells are a subset that have been found to express the transcription factor T-bet. T-bet is associated with class switching. T-bet B cells are also thought to be important in immune responses against intracellular bacterial and viral infections. [21]

Vaccination

Vaccines are based on the notion of immunological memory. The preventative injection of a non-pathogenic antigen into the organism allows the body to generate a durable immunological memory. The injection of the antigen leads to an antibody response followed by the production of memory B cells. These memory B cells are promptly reactivated upon infection with the antigen and can effectively protect the organism from disease. [22]

Long-lived plasma cells and memory B cells are responsible for the long-term humoral immunity elicited by most vaccines. An experiment has been carried in order to observe the longevity of memory B cells after vaccination, in this case with the smallpox vaccine (DryVax), which was selected due to the fact that smallpox was eradicated, so the immune memory to smallpox is a useful benchmark to understand the longevity of the immune memory B cells in the absence of restimulation. The study concluded that the specific memory B cells are maintained for decades, indicating that the immunological memory is long-lived in the B cell compartment after a robust initial antigen exposure. [23]

See also

Related Research Articles

<span class="mw-page-title-main">Antibody</span> Protein(s) forming a major part of an organisms immune system

An antibody (Ab) is the secreted form of a B cell receptor; the term immunoglobulin (Ig) can refer to either the membrane-bound form or the secreted form of the B cell receptor, but they are, broadly speaking, the same protein, and so the terms are often treated as synonymous. Antibodies are large, Y-shaped proteins belonging to the immunoglobulin superfamily which are used by the immune system to identify and neutralize foreign objects such as bacteria and viruses, including those that cause disease. Antibodies can recognize virtually any size antigen with diverse chemical compositions from molecules. Each antibody recognizes one or more specific antigens. This term literally means "antibody generator", as it is the presence of an antigen that drives the formation of an antigen-specific antibody. Each tip of the "Y" of an antibody contains a paratope that specifically binds to one particular epitope on an antigen, allowing the two molecules to bind together with precision. Using this mechanism, antibodies can effectively "tag" a microbe or an infected cell for attack by other parts of the immune system, or can neutralize it directly.

<span class="mw-page-title-main">B cell</span> Type of white blood cell

B cells, also known as B lymphocytes, are a type of white blood cell of the lymphocyte subtype. They function in the humoral immunity component of the adaptive immune system. B cells produce antibody molecules which may be either secreted or inserted into the plasma membrane where they serve as a part of B-cell receptors. When a naïve or memory B cell is activated by an antigen, it proliferates and differentiates into an antibody-secreting effector cell, known as a plasmablast or plasma cell. In addition, B cells present antigens and secrete cytokines. In mammals, including marsupials B cells mature in the bone marrow, which is at the core of most bones. In birds, B cells mature in the bursa of Fabricius, a lymphoid organ where they were first discovered by Chang and Glick, which is why the B stands for bursa and not bone marrow, as commonly believed.

Humoral immunity is the aspect of immunity that is mediated by macromolecules – including secreted antibodies, complement proteins, and certain antimicrobial peptides – located in extracellular fluids. Humoral immunity is named so because it involves substances found in the humors, or body fluids. It contrasts with cell-mediated immunity. Humoral immunity is also referred to as antibody-mediated immunity.

<span class="mw-page-title-main">Plasma cell</span> White blood cell that secretes large volumes of antibodies

Plasma cells, also called plasma B cells or effector B cells, are white blood cells that originate in the lymphoid organs as B cells and secrete large quantities of proteins called antibodies in response to being presented specific substances called antigens. These antibodies are transported from the plasma cells by the blood plasma and the lymphatic system to the site of the target antigen, where they initiate its neutralization or destruction. B cells differentiate into plasma cells that produce antibody molecules closely modeled after the receptors of the precursor B cell.

<span class="mw-page-title-main">Adaptive immune system</span> Subsystem of the immune system

The adaptive immune system, also known as the acquired immune system, or specific immune system is a subsystem of the immune system that is composed of specialized, systemic cells and processes that eliminate pathogens or prevent their growth. The acquired immune system is one of the two main immunity strategies found in vertebrates.

Gut-associated lymphoid tissue (GALT) is a component of the mucosa-associated lymphoid tissue (MALT) which works in the immune system to protect the body from invasion in the gut.

<span class="mw-page-title-main">CD40 (protein)</span> Mammalian protein found in humans

Cluster of differentiation 40, CD40 is a type I transmembrane protein found on antigen-presenting cells and is required for their activation. The binding of CD154 (CD40L) on TH cells to CD40 activates antigen presenting cells and induces a variety of downstream effects.

<span class="mw-page-title-main">Germinal center</span> Lymphatic tissue structure

Germinal centers or germinal centres (GCs) are transiently formed structures within B cell zone (follicles) in secondary lymphoid organs – lymph nodes, ileal Peyer's patches, and the spleen – where mature B cells are activated, proliferate, differentiate, and mutate their antibody genes during a normal immune response; most of the germinal center B cells (BGC) are removed by tingible body macrophages. There are several key differences between naive B cells and GC B cells, including level of proliferative activity, size, metabolic activity and energy production. The B cells develop dynamically after the activation of follicular B cells by T-dependent antigen. The initiation of germinal center formation involves the interaction between B and T cells in the interfollicular area of the lymph node, CD40-CD40L ligation, NF-kB signaling and expression of IRF4 and BCL6.

<span class="mw-page-title-main">Immune complex</span> Molecule formed binding antigens to antibodies

An immune complex, sometimes called an antigen-antibody complex or antigen-bound antibody, is a molecule formed from the binding of multiple antigens to antibodies. The bound antigen and antibody act as a unitary object, effectively an antigen of its own with a specific epitope. After an antigen-antibody reaction, the immune complexes can be subject to any of a number of responses, including complement deposition, opsonization, phagocytosis, or processing by proteases. Red blood cells carrying CR1-receptors on their surface may bind C3b-coated immune complexes and transport them to phagocytes, mostly in liver and spleen, and return to the general circulation.

<span class="mw-page-title-main">B-cell receptor</span> Transmembrane protein on the surface of a B cell

The B-cell receptor (BCR) is a transmembrane protein on the surface of a B cell. A B-cell receptor is composed of a membrane-bound immunoglobulin molecule and a signal transduction moiety. The former forms a type 1 transmembrane receptor protein, and is typically located on the outer surface of these lymphocyte cells. Through biochemical signaling and by physically acquiring antigens from the immune synapses, the BCR controls the activation of the B cell. B cells are able to gather and grab antigens by engaging biochemical modules for receptor clustering, cell spreading, generation of pulling forces, and receptor transport, which eventually culminates in endocytosis and antigen presentation. B cells' mechanical activity adheres to a pattern of negative and positive feedbacks that regulate the quantity of removed antigen by manipulating the dynamic of BCR–antigen bonds directly. Particularly, grouping and spreading increase the relation of antigen with BCR, thereby proving sensitivity and amplification. On the other hand, pulling forces delinks the antigen from the BCR, thus testing the quality of antigen binding.

<span class="mw-page-title-main">Polyclonal B cell response</span> Immune response by adaptive immune system

Polyclonal B cell response is a natural mode of immune response exhibited by the adaptive immune system of mammals. It ensures that a single antigen is recognized and attacked through its overlapping parts, called epitopes, by multiple clones of B cell.

<span class="mw-page-title-main">CD19</span> Biomarker for B cell lineage

B-lymphocyte antigen CD19, also known as CD19 molecule, B-Lymphocyte Surface Antigen B4, T-Cell Surface Antigen Leu-12 and CVID3 is a transmembrane protein that in humans is encoded by the gene CD19. In humans, CD19 is expressed in all B lineage cells. Contrary to some early doubts, human plasma cells do express CD19, as confirmed by others. CD19 plays two major roles in human B cells: on the one hand, it acts as an adaptor protein to recruit cytoplasmic signaling proteins to the membrane; on the other, it works within the CD19/CD21 complex to decrease the threshold for B cell receptor signaling pathways. Due to its presence on all B cells, it is a biomarker for B lymphocyte development, lymphoma diagnosis and can be utilized as a target for leukemia immunotherapies.

B1 cells are a sub-class of B cell lymphocytes that are involved in the humoral immune response. They are not part of the adaptive immune system, as they have no memory, but otherwise, B1 cells perform many of the same roles as other B cells: making antibodies against antigens and acting as antigen-presenting cells. These B1 cells are commonly found in peripheral sites, but less commonly found in the blood. These cells are involved in antibody response during an infection or vaccination.

<span class="mw-page-title-main">GPR183</span> Protein-coding gene in the species Homo sapiens

G-protein coupled receptor 183 also known as Epstein-Barr virus-induced G-protein coupled receptor 2 (EBI2) is a protein (GPCR) expressed on the surface of some immune cells, namely B cells and T cells; in humans it is encoded by the GPR183 gene. Expression of EBI2 is one critical mediator of immune cell localization within lymph nodes, responsible in part for the coordination of B cell, T cell, and dendritic cell movement and interaction following antigen exposure. EBI2 is a receptor for oxysterols. The most potent activator is 7α,25-dihydroxycholesterol (7α,25-OHC), with other oxysterols exhibiting varying affinities for the receptor. Oxysterol gradients drive chemotaxis, attracting the EBI2-expressing cells to locations of high ligand concentration. The GPR183 gene was identified due to its upregulation during Epstein-Barr virus infection of the Burkitt's lymphoma cell line BL41, hence its name: EBI2.

<span class="mw-page-title-main">FCGR2B</span>

Fc fragment of IgG receptor IIb is a low affinity inhibitory receptor for the Fc region of immunoglobulin gamma (IgG). FCGR2B participates in the phagocytosis of immune complexes and in the regulation of antibody production by B lymphocytes.

<span class="mw-page-title-main">Marginal-zone B cell</span>

Marginal-zone B cells are noncirculating mature B cells that in humans segregate anatomically into the marginal zone (MZ) of the spleen and certain other types of lymphoid tissue. The MZ B cells within this region typically express low-affinity polyreactive B-cell receptors (BCR), high levels of IgM, Toll-like receptors (TLRs), CD21, CD1, CD9, CD27 with low to negligible levels of secreted-IgD, CD23, CD5, and CD11b that help to distinguish them phenotypically from follicular (FO) B cells and B1 B cells.

<span class="mw-page-title-main">Follicular B helper T cells</span>

Follicular helper T cells (also known as T follicular helper cells and abbreviated as TFH), are antigen-experienced CD4+ T cells found in the periphery within B cell follicles of secondary lymphoid organs such as lymph nodes, spleen and Peyer's patches, and are identified by their constitutive expression of the B cell follicle homing receptor CXCR5. Upon cellular interaction and cross-signaling with their cognate follicular (Fo B) B cells, TFH cells trigger the formation and maintenance of germinal centers through the expression of CD40 ligand (CD40L) and the secretion of IL-21 and IL-4. TFH cells also migrate from T cell zones into these seeded germinal centers, predominantly composed of rapidly dividing B cells mutating their Ig genes. Within germinal centers, TFH cells play a critical role in mediating the selection and survival of B cells that go on to differentiate either into long-lived plasma cells capable of producing high affinity antibodies against foreign antigen, or germinal center-dependent memory B cells capable of quick immune re-activation in the future if ever the same antigen is re-encountered. TFH cells are also thought to facilitate negative selection of potentially autoimmune-causing mutated B cells in the germinal center. However, the biomechanisms by which TFH cells mediate germinal center tolerance are yet to be fully understood.

Gene expression profiling has revealed that diffuse large B-cell lymphoma (DLBCL) is composed of at least 3 different sub-groups, each having distinct oncogenic mechanisms that respond to therapies in different ways. Germinal Center B-Cell like (GCB) DLBCLs appear to arise from normal germinal center B cells, while Activated B-cell like (ABC) DLBCLs are thought to arise from postgerminal center B cells that are arrested during plasmacytic differentiation. The differences in gene expression between GCB DLBCL and ABC DLBCL are as vast as the differences between distinct types of leukemia, but these conditions have historically been grouped together and treated as the same disease.

<span class="mw-page-title-main">Centroblast</span>

A centroblast generally refers to an activated B cell that is enlarged and is rapidly proliferating in the germinal center of a lymphoid follicle. They are specifically located in the dark zone of the germinal center. Centroblasts form from naive B cells being exposed to follicular dendritic cell cytokines, such as IL-6, IL-15, 8D6, and BAFF. Stimulation from helper T cells is also required for centroblast development. Interaction between CD40 ligand on an activated T helper cell and the B cell CD40 receptor induces centroblasts to express activation-induced cytidine deaminase, leading to somatic hypermutation, allowing the B cell receptor to potentially gain stronger affinity for an antigen. In the absence of FDC and helper T cell stimulation, centroblasts are unable to differentiate and will undergo CD95-mediated apoptosis.

Long-lived plasma cells (LLPCs) are a distinct subset of plasma cells that play a crucial role in maintaining humoral memory and long-term immunity. They continuously produce and secrete high-affinity antibodies into the bloodstream, conversely to memory B cells, which are quiescent and respond quickly to antigens upon recall.

References

  1. ↑ Crotty S, Felgner P, Davies H, Glidewell J, Villarreal L, Ahmed R (November 2003). "Cutting edge: long-term B cell memory in humans after smallpox vaccination". Journal of Immunology. 171 (10): 4969–4973. doi: 10.4049/jimmunol.171.10.4969 . PMID   14607890.
  2. 1 2 3 4 5 Weisel F, Shlomchik M (April 2017). "Memory B Cells of Mice and Humans". Annual Review of Immunology. 35 (1): 255–284. doi: 10.1146/annurev-immunol-041015-055531 . PMID   28142324.
  3. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 Seifert M, Küppers R (December 2016). "Human memory B cells". Leukemia. 30 (12): 2283–2292. doi:10.1038/leu.2016.226. PMID   27499139. S2CID   28936531.
  4. 1 2 3 4 5 6 7 8 9 10 11 12 Kurosaki T, Kometani K, Ise W (March 2015). "Memory B cells". Nature Reviews. Immunology. 15 (3): 149–159. doi:10.1038/nri3802. PMID   25677494. S2CID   20825732.
  5. 1 2 Garside P, Ingulli E, Merica RR, Johnson JG, Noelle RJ, Jenkins MK (July 1998). "Visualization of specific B and T lymphocyte interactions in the lymph node". Science. 281 (5373): 96–99. Bibcode:1998Sci...281...96G. doi:10.1126/science.281.5373.96. PMID   9651253.
  6. 1 2 3 4 5 6 7 8 Suan D, Sundling C, Brink R (April 2017). "Plasma cell and memory B cell differentiation from the germinal center". Current Opinion in Immunology. Lymphocyte development and activation * Tumour immunology. 45: 97–102. doi:10.1016/j.coi.2017.03.006. PMID   28319733.
  7. 1 2 Taylor JJ, Jenkins MK, Pape KA (December 2012). "Heterogeneity in the differentiation and function of memory B cells". Trends in Immunology. 33 (12): 590–597. doi:10.1016/j.it.2012.07.005. PMC   3505266 . PMID   22920843.
  8. ↑ Phan TG, Tangye SG (April 2017). "Memory B cells: total recall". Current Opinion in Immunology. Lymphocyte development and activation * Tumour immunology. 45: 132–140. doi:10.1016/j.coi.2017.03.005. PMID   28363157.
  9. ↑ Allman D, Wilmore JR, Gaudette BT (March 2019). "The continuing story of T-cell independent antibodies". Immunological Reviews. 288 (1): 128–135. doi:10.1111/imr.12754. PMC   6653682 . PMID   30874357.
  10. ↑ Victora GD, Nussenzweig MC (2012-03-26). "Germinal centers". Annual Review of Immunology. 30 (1): 429–457. doi:10.1146/annurev-immunol-020711-075032. PMID   22224772. S2CID   20168324.
  11. 1 2 3 Shinnakasu R, Kurosaki T (April 2017). "Regulation of memory B and plasma cell differentiation". Current Opinion in Immunology. Lymphocyte development and activation * Tumour immunology. 45: 126–131. doi:10.1016/j.coi.2017.03.003. PMID   28359033.
  12. ↑ Gatto D, Brink R (November 2010). "The germinal center reaction". The Journal of Allergy and Clinical Immunology. 126 (5): 898–907, quiz 908–9. doi: 10.1016/j.jaci.2010.09.007 . PMID   21050940.
  13. ↑ Zuccarino-Catania, Griselda V; Sadanand, Saheli; Weisel, Florian J; Tomayko, Mary M; Meng, Hailong; Kleinstein, Steven H; Good-Jacobson, Kim L; Shlomchik, Mark J (July 2014). "CD80 and PD-L2 define functionally distinct memory B cell subsets that are independent of antibody isotype". Nature Immunology. 15 (7): 631–637. doi:10.1038/ni.2914. ISSN   1529-2908. PMC   4105703 . PMID   24880458.
  14. ↑ Chong, Anita S.; Ansari, M. Javeed (April 2018). "Heterogeneity of memory B cells". American Journal of Transplantation. 18 (4): 779–784. doi:10.1111/ajt.14669. PMC   5962275 . PMID   29359404.
  15. ↑ Anderson SM, Hannum LG, Shlomchik MJ (April 2006). "Memory B cell survival and function in the absence of secreted antibody and immune complexes on follicular dendritic cells". Journal of Immunology. 176 (8): 4515–4519. doi: 10.4049/jimmunol.176.8.4515 . PMID   16585539. S2CID   85927231.
  16. ↑ Jones DD, Wilmore JR, Allman D (November 2015). "Cellular Dynamics of Memory B Cell Populations: IgM+ and IgG+ Memory B Cells Persist Indefinitely as Quiescent Cells". Journal of Immunology. 195 (10): 4753–4759. doi:10.4049/jimmunol.1501365. PMC   4637268 . PMID   26438523.
  17. ↑ Komegae, Evilin Naname; Grund, Lidiane Zito; Lopes-Ferreira, Monica; Lima, Carla (2013-08-05). Richard, Yolande (ed.). "TLR2, TLR4 and the MyD88 Signaling Are Crucial For the In Vivo Generation and the Longevity of Long-Lived Antibody-Secreting Cells". PLOS ONE. 8 (8): e71185. Bibcode:2013PLoSO...871185K. doi: 10.1371/journal.pone.0071185 . ISSN   1932-6203. PMC   3733974 . PMID   23940714.
  18. ↑ Elgueta, Raul; Marks, Ellen; Nowak, Elizabeth; Menezes, Shinelle; Benson, Micah; Raman, Vanitha S.; Ortiz, Carla; O’Connell, Samuel; Hess, Henry; Lord, Graham M.; Noelle, Randolph (2015-01-15). "CCR6-Dependent Positioning of Memory B Cells Is Essential for Their Ability To Mount a Recall Response to Antigen". The Journal of Immunology. 194 (2): 505–513. doi:10.4049/jimmunol.1401553. ISSN   0022-1767. PMC   4282958 . PMID   25505290.
  19. ↑ Pupovac A, Good-Jacobson KL (April 2017). "An antigen to remember: regulation of B cell memory in health and disease". Current Opinion in Immunology. Lymphocyte development and activation * Tumour immunology. 45: 89–96. doi:10.1016/j.coi.2017.03.004. PMC   7126224 . PMID   28319732.
  20. ↑ Montecino-Rodriguez E, Dorshkind K (January 2012). "B-1 B cell development in the fetus and adult". Immunity. 36 (1): 13–21. doi:10.1016/j.immuni.2011.11.017. PMC   3269035 . PMID   22284417.
  21. ↑ Knox JJ, Myles A, Cancro MP (March 2019). "T-bet+ memory B cells: Generation, function, and fate". Immunological Reviews. 288 (1): 149–160. doi:10.1111/imr.12736. PMC   6626622 . PMID   30874358.
  22. ↑ Dhenni R, Phan TG (July 2020). "The geography of memory B cell reactivation in vaccine-induced immunity and in autoimmune disease relapses". Immunological Reviews. 296 (1): 62–86. doi:10.1111/imr.12862. PMID   32472583. S2CID   219103939.
  23. ↑ Crotty, Shane; Felgner, Phil; Davies, Huw; Glidewell, John; Villarreal, Luis; Ahmed, Rafi (2003-11-15). "Cutting Edge: Long-Term B Cell Memory in Humans after Smallpox Vaccination". The Journal of Immunology. 171 (10): 4969–4973. doi: 10.4049/jimmunol.171.10.4969 . ISSN   0022-1767. PMID   14607890. S2CID   32215286.
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