B-1 cell

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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. [1]

Contents

There are two types of B1 cells subsets, B1a cells and B1b cells. [1] B1b cells have been shown to be capable of memory responses. [2] B1b cells also can recognize protective antigens in bacteria, which is unique because they are targeting something internal. [1]

Origin

B1 cells are first produced in the fetus and most B1 cells undergo self-renewal in the periphery, unlike conventional B cells (B2 cells) that are produced after birth and replaced in the bone marrow.

Types

Human B1 cells have been found to have marker profile of CD20+CD27+CD43+CD70- and could either be CD5+ or CD5-, which has been debated since. [3] CD5-CD72 is thought to mediate B cell-B cell interaction. What differentiates B1 cells from other B cells is the variable existence of CD5, CD86, IgM and IgD. [1] B-1 B cells, in the mouse, can be further subdivided into B-1a (CD5+) and B-1b (CD5) subtypes. Unlike B1a B cells, the B-1b subtype can be generated from precursors in the adult bone marrow. The B1a and B1b precursors have been reported to differ in the expression levels of CD138. [4]

Compared to B1a cells, B1b cells seem to recognize more types of antigens including intracellular antigens. Previously, B1b cell antigen recognition was thought to be random; however, recent research indicated that B1b cells specifically target a variety of protective antigens, also called conserved factors, over other types antigens. [1]

Recent functional studies indicate a further subdivision of labor assigning B1a cells as the producers of natural serum antibody (7). In contrast, B1b cells appear to be the primary source of dynamic T cell independent (TI) antibody production and long-term protection after bacterial infection such as Borrelia hermsii [2] and Streptococcus pneumoniae . [5] These studies indicate preexisting subset differences in B-cell receptor (BCR) specificity and antigen-driven B cell fate that remain important unresolved features of the system.

Role in immune response

B1b cells are the most common B cells involved in antibody response during an infection or vaccination. This is because they can respond without receiving an activation signal from a T Helper cell. [1]

B1 cells express IgM in greater quantities than IgG and its receptors show polyspecificity, meaning that they have low affinities for many different antigens. These polyspecific immunoglobulins often have a preference for other immunoglobulins, self antigens and common bacterial polysaccharides. B1 cells are present in low numbers in the lymph nodes and spleen and are instead found predominantly in the peritoneal and pleural cavities. B1 cells generate diversity mainly via recombinatorial recombination (there is a preferential recombination between D-proximal VH gene segments).[ citation needed ]

B1 cells characteristically express high levels of surface IgM (sIgM), demonstrable CD11b, and low levels of surface IgD (sIgD), CD21, CD23, and the B cell isoform of CD45R (B220). [6] In adult mice, B1 cells constitute a minor fraction of the spleen and secondary lymphoid tissues but are enriched in the pleural and peritoneal cavities. [7] , [8] B1 cells were shown to arise from precursors in the fetal liver and neonatal but not adult bone marrow and constitute the earliest wave of mature peripheral B cells.

B1 cells express a separable BCR repertoire. [9] Sequence analysis indicates antibodies with restricted sets of V region genes and an increased usage of λ light chains. [10] B1 cells sequences also show no evidence for somatic hypermutation (SHM), and few non-templated nucleotide (N) sequence insertions, a pattern typical of neonatal B cells. Efficient B1 B cell development appears to be dependent on positive regulators of BCR signaling and the loss of negative regulators promotes greater accumulation of B1 B cells. [11] Hence, there appears to be a role for self or foreign antigen in shaping the repertoire of the B-1 B cell compartment. [12]

B1 cells self-renew and spontaneously secrete IgM and IgG3 serum antibodies. These natural serum antibodies display extensive polyreactivity, demonstrable self-reactivity and bind to many common pathogen-associated carbohydrates. [9] Natural serum antibodies play an important early role in the immune response to many bacteria and viruses but require complement fixation for effective antigen clearance. Innate sensing mechanisms can rapidly mobilize B1 cells regardless of specificity, highlighting the innate-like activity of this separate B cell compartment.[ citation needed ]

B1b cells are known to be able to induce some type of memory, but their role in memory cells is unknown and may follow an untraditional route. [1]

B1b cells have effective and long-lasting responses to Borrelia hermsii , Streptococcus pneumoniae , Salmonella Enterica , Salmonella Typhi and Enterobacter cloacae bacteria. [1]

Laboratory isolation

In research laboratories, B1 B cells can be easily isolated from a mouse by injecting cell medium or PBS into the peritoneal cavity of the mouse and then draining it off via a technique mirroring diagnostic peritoneal lavage. Cells can be identified and placed into two categories "B1a" or B1b" using flow cytometry looking for surface expression of CD19, B220, and CD5. B1a expresses high CD5 level, while B1b expresses low CD5 to almost-absent levels; both are CD19+ and B220low/-.[ citation needed ]

Related Research Articles

Antibody Immune system protein

An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of the pathogen, called an antigen. Each tip of the "Y" of an antibody contains a paratope that is specific for one particular epitope on an antigen, allowing these two structures to bind together with precision. Using this binding mechanism, an antibody can tag a microbe or an infected cell for attack by other parts of the immune system, or can neutralize it directly.

Immunology Branch of medicine studying the immune system

Immunology is a branch of biology that covers the study of immune systems in all organisms. Immunology charts, measures, and contextualizes the physiological functioning of the immune system in states of both health and diseases; malfunctions of the immune system in immunological disorders ; and the physical, chemical, and physiological characteristics of the components of the immune system in vitro, in situ, and in vivo. Immunology has applications in numerous disciplines of medicine, particularly in the fields of organ transplantation, oncology, rheumatology, virology, bacteriology, parasitology, psychiatry, and dermatology.

B cell 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; however, these antibodies are not secreted. Rather, they are 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. Additionally, B cells present antigens and secrete cytokines. In mammals, 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.

Natural killer cell Type of cytotoxic lymphocyte

Natural killer cells, also known as NK cells or large granular lymphocytes (LGL), are a type of cytotoxic lymphocyte critical to the innate immune system that belong to the rapidly expanding family of innate lymphoid cells (ILC) and represent 5–20% of all circulating lymphocytes in humans. The role of NK cells is analogous to that of cytotoxic T cells in the vertebrate adaptive immune response. NK cells provide rapid responses to virus-infected cell and other intracellular pathogens acting at around 3 days after infection, and respond to tumor formation. Typically, immune cells detect the major histocompatibility complex (MHC) presented on infected cell surfaces, triggering cytokine release, causing the death of the infected cell by lysis or apoptosis. NK cells are unique, however, as they have the ability to recognize and kill stressed cells in the absence of antibodies and MHC, allowing for a much faster immune reaction. They were named "natural killers" because of the notion that they do not require activation to kill cells that are missing "self" markers of MHC class 1. This role is especially important because harmful cells that are missing MHC I markers cannot be detected and destroyed by other immune cells, such as T lymphocyte cells.

Lymphocyte Subtype of white blood cell

A lymphocyte is a type of white blood cell in the immune system of jawed vertebrates. Lymphocytes include natural killer cells, T cells, and B cells. They are the main type of cell found in lymph, which prompted the name "lymphocyte".

Immunoglobulin G (IgG) is a type of antibody. Representing approximately 75% of serum antibodies in humans, IgG is the most common type of antibody found in blood circulation. IgG molecules are created and released by plasma B cells. Each IgG antibody has two paratopes.

Immunoglobulin A Antibody that plays a crucial role in the immune function of mucous membranes

Immunoglobulin A is an antibody that plays a crucial role in the immune function of mucous membranes. The amount of IgA produced in association with mucosal membranes is greater than all other types of antibody combined. In absolute terms, between three and five grams are secreted into the intestinal lumen each day. This represents up to 15% of total immunoglobulins produced throughout the body.

Immunoglobulin D

Immunoglobulin D (IgD) is an antibody isotype that makes up about 1% of proteins in the plasma membranes of immature B-lymphocytes where it is usually co-expressed with another cell surface antibody called IgM. IgD is also produced in a secreted form that is found in very small amounts in blood serum, representing 0.25% of immunoglobulins in serum. The relative molecular mass and half-life of secreted IgD is 185 kDa and 2.8 days, respectively. Secreted IgD is produced as a monomeric antibody with two heavy chains of the delta (δ) class, and two Ig light chains.

Immunoglobulin E Immunoglobulin E (IgE) Antibody

Immunoglobulin E (IgE) is a type of antibody that has been found only in mammals. IgE is synthesised by plasma cells. Monomers of IgE consist of two heavy chains and two light chains, with the ε chain containing 4 Ig-like constant domains (Cε1-Cε4). IgE is thought to be an important part of the immune response against infection by certain parasitic worms, including Schistosoma mansoni, Trichinella spiralis, and Fasciola hepatica. IgE is also utilized during immune defense against certain protozoan parasites such as Plasmodium falciparum. IgE may have evolved as a defense to protect against venoms.

Memory B cell

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. 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. 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.

Opsonins are proteins of the innate and adaptive immune system that facilitate phagocytosis and cell lysis by “marking” antigens. Opsonization, then, is the modification of antigens by opsonins to make them more accessible to phagocytic cells and other immune cells. Opsonins bind to antigen and are recognized by receptors on immune cells.

Adaptive immune system Subsystem of the immune system that is composed of specialized, systemic cells and processes

The adaptive immune system, also referred as the acquired 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.

Marginal zone

The marginal zone is the region at the interface between the non-lymphoid red pulp and the lymphoid white-pulp of the spleen.

Immune complex

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.

B-cell receptor

The B cell receptor (BCR) is a transmembrane protein on the surface of a B cell. B cell receptors are composed of immunoglobulin molecules that form a type 1 transmembrane receptor protein, and are 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.

CD19

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.

Isotype (immunology)

In immunology, antibodies are classified into several types called isotypes or classes. The variable (V) regions near the tip of the antibody can differ from molecule to molecule in countless ways, allowing it to specifically target an antigen . In contrast, the constant (C) regions only occur in a few variants, which define the antibody's class. Antibodies of different classes activate distinct effector mechanisms in response to an antigen . They appear at different stages of an immune response, differ in structural features, and in their location around the body.

FCGR2B

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.

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.

The immune network theory is a theory of how the adaptive immune system works, that has been developed since 1974 mainly by Niels Jerne and Geoffrey W. Hoffmann. The theory states that the immune system is an interacting network of lymphocytes and molecules that have variable (V) regions. These V regions bind not only to things that are foreign to the vertebrate, but also to other V regions within the system. The immune system is therefore seen as a network, with the components connected to each other by V-V interactions.

References

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