Clone (cell biology)

Last updated
Clonal expansion and monoclonal versus polyclonal proliferation Clonal expansion and monoclonal versus polyclonal proliferation.PNG
Clonal expansion and monoclonal versus polyclonal proliferation

A clone is a group of identical cells that share a common ancestry, meaning they are derived from the same cell. [1]

Contents

Clonality implies the state of a cell or a substance being derived from one source or the other. Thus there are terms like polyclonal—derived from many clones; oligoclonal [2] —derived from a few clones; and monoclonal—derived from one clone. These terms are most commonly used in context of antibodies or immunocytes.

Contexts

This concept of clone assumes importance as all the cells that form a clone share common ancestry, which has a very significant consequence: shared genotype.

  1. One of the most prominent usage is in describing a clone of B cells. The B cells in the body have two important phenotypes (functional forms)—the antibody secreting, terminally differentiated (that is, they cannot divide further) plasma cells, and the memory and the naive cells—both of which retain their proliferative potential.
  2. Another important area where one can talk of "clones" of cells is neoplasms. [3] Many of the tumors derive from one (sufficiently) mutated cell, so they are technically a single clone of cells. However, during course of cell division, one of the cells can get mutated further and acquire new characteristics to diverge as a new clone. However, this view of cancer onset has been challenged in recent years and many tumors have been argued to have polyclonal origin, [4] i.e. derived from two or more cells or clones, including malignant mesothelioma. [5]
  3. All the granulosa cells in a Graafian follicle are in fact clones.
  4. Paroxysmal nocturnal hemoglobinuria is a disorder of bone marrow cells resulting in shortened life of red blood cells, which is also a result of clonal expansion, i.e., all the altered cells are originally derived from a single cell, which also somewhat compromises the functioning of other "normal" bone marrow cells. [6]

Basis of clonal proliferation

Most other cells cannot divide indefinitely as after a few cycles of cell division the cells stop expressing an enzyme telomerase. The genetic material, in the form of deoxyribonucleic acid (DNA), continues to shorten with each cell division, and cells eventually stop dividing when they sense that their DNA is critically shortened. However, this enzyme in "youthful" cells replaces these lost bits (nucleotides) of DNA, thus making almost unlimited cycles of cell division possible. It is believed that the above-mentioned tissues have a constitutional elevated expression of telomerase. When ultimately many cells are produced by a single cell, clonal expansion is said to have taken place.

Concept of clonal colony

A somewhat similar concept is that of a clonal colony (also called a genet), wherein the cells (usually unicellular) also share a common ancestry, but which also requires the products of clonal expansion to reside at "one place", or in close proximity. A clonal colony would be well exemplified by a bacterial culture colony, or the bacterial films that are more likely to be found in vivo (e.g., in infected multicellular hosts). Whereas, the cells of clones dealt with here are specialized cells of a multicellular organism (usually vertebrates), and reside at quite distant places. For instance, two plasma cells belonging to the same clone could be derived from different memory cells (in turn with shared clonality) and could be residing in quite distant locations, such as the cervical (in the neck) and inguinal (in the groin) lymph nodes.

See also

Related Research Articles

Immunosuppressive drug agent that suppresses immune function by one of several mechanisms of action (e.g. inhibiting DNA synthesis, inhibiting activation of T-cells, or inhibiting the activation of helper cells)

Immunosuppressive drugs, also known as immunosuppressive agents, immunosuppressants and antirejection medications are drugs that inhibit or prevent activity of the immune system.

Telomerase Telomere-restoring protein active in the most rapidly dividing cells

Telomerase, also called terminal transferase, is a ribonucleoprotein that adds a species-dependent telomere repeat sequence to the 3' end of telomeres. A telomere is a region of repetitive sequences at each end of eukaryotic chromosomes in most eukaryotes. Telomeres protect the end of the chromosome from DNA damage or from fusion with neighbouring chromosomes. The fruit fly Drosophila melanogaster lacks telomerase, but instead uses retrotransposons to maintain telomeres.

Carcinoma A category of types of cancer that develops from epithelial cells

Carcinoma is a category of types of cancer that develop from epithelial cells. Specifically, a carcinoma is a cancer that begins in a tissue that lines the inner or outer surfaces of the body, and that arises from cells originating in the endodermal, mesodermal or ectodermal germ layer during embryogenesis.

Mesothelioma Cancer associated with asbestos

Mesothelioma is a type of cancer that develops from the thin layer of tissue that covers many of the internal organs. The most common area affected is the lining of the lungs and chest wall. Less commonly the lining of the abdomen and rarely the sac surrounding the heart, or the sac surrounding the testis may be affected. Signs and symptoms of mesothelioma may include shortness of breath due to fluid around the lung, a swollen abdomen, chest wall pain, cough, feeling tired, and weight loss. These symptoms typically come on slowly.

Post-transplant lymphoproliferative disorder (PTLD) is the name given to a B-cell proliferation due to therapeutic immunosuppression after organ transplantation. These patients may develop infectious mononucleosis-like lesions or polyclonal polymorphic B-cell hyperplasia. Some of these B-cells may undergo mutations which will render them malignant, giving rise to a lymphoma.

Hybridoma technology

Hybridoma technology is a method for producing large numbers of identical antibodies. This process starts by injecting a mouse with an antigen that provokes an immune response. A type of white blood cell, the B cell, produces antibodies that bind to the injected antigen. These antibody producing B-cells are then harvested from the mouse and, in turn, fused with immortal B cell cancer cells, a myeloma, to produce a hybrid cell line called a hybridoma, which has both the antibody-producing ability of the B-cell and the longevity and reproductivity of the myeloma. The hybridomas can be grown in culture, each culture starting with one viable hybridoma cell, producing cultures each of which consists of genetically identical hybridomas which produce one antibody per culture (monoclonal) rather than mixtures of different antibodies (polyclonal). The myeloma cell line that is used in this process is selected for its ability to grow in tissue culture and for an absence of antibody synthesis. In contrast to polyclonal antibodies, which are mixtures of many different antibody molecules, the monoclonal antibodies produced by each hybridoma line are all chemically identical.

Neoplasm Abnormal mass of tissue as a result of abnormal growth or division of cells

A neoplasm is a type of abnormal and excessive growth, called neoplasia, of tissue. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and it persists growing abnormally, even if the original trigger is removed. This abnormal growth usually forms a mass. When it forms a mass, it may be called a tumor.

Carcinogenesis, also called oncogenesis or tumorigenesis, is the formation of a cancer, whereby normal cells are transformed into cancer cells. The process is characterized by changes at the cellular, genetic, and epigenetic levels and abnormal cell division. Cell division is a physiological process that occurs in almost all tissues and under a variety of circumstances. Normally the balance between proliferation and programmed cell death, in the form of apoptosis, is maintained to ensure the integrity of tissues and organs. According to the prevailing accepted theory of carcinogenesis, the somatic mutation theory, mutations in DNA and epimutations that lead to cancer disrupt these orderly processes by disrupting the programming regulating the processes, upsetting the normal balance between proliferation and cell death. This results in uncontrolled cell division and the evolution of those cells by natural selection in the body. Only certain mutations lead to cancer whereas the majority of mutations do not.

Dyskeratosis congenita rare progressive congenital disorder with a highly variable phenotype

Dyskeratosis congenita (DKC),also known as zinsser-engman-cole syndrome is a rare progressive congenital disorder with a highly variable phenotype. The entity was classically defined by the triad of abnormal skin pigmentation, nail dystrophy, and leukoplakia of the oral mucosa, but these components do not always occur. DKC is characterized by short telomeres. Some of the manifestations resemble premature aging. The disease initially mainly affects the skin, but a major consequence is progressive bone marrow failure which occurs in over 80%, causing early mortality.

Polyclonal B cell response

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.

Plasma cell dyscrasias are a spectrum of progressively more severe monoclonal gammopathies in which a clone or multiple clones of pre-malignant or malignant plasma cells over-produce and secrete into the blood stream a myeloma protein, i.e. an abnormal monoclonal antibody or portion thereof. The exception to this rule is the disorder termed non-secretory multiple myeloma; this disorder is a form of plasma cell dyscrasia in which no myeloma protein is detected in serum or urine of individuals who have clear evidence of an increase in clonal bone marrow plasma cells and/or evidence of clonal plasma cell-mediated tissue injury. Here, a clone of plasma cells refers to group of plasma cells that are abnormal in that they have an identical genetic identity and therefore are descendants of a single genetically distinct ancestor cell.

Somatic evolution is the accumulation of mutations and epimutations in somatic cells during a lifetime, and the effects of those mutations and epimutations on the fitness of those cells. This evolutionary process has first been shown by the studies of Bert Vogelstein in colon cancer. Somatic evolution is important in the process of aging as well as the development of some diseases, including cancer.

Symphogen is a biotechnology company located in Copenhagen, Denmark that develops protein drugs based on recombinant monoclonal antibody mixtures. These drugs are different from the polyclonal antibodies, as each antibody in the mixture is produced from one carefully selected clone. Their three main areas of therapeutic research are immunoglobulin replacement, cancer, and infectious diseases. The company was founded in 2000 and has patents on a drug discovery platform called Symplex and a drug manufacturing platform called Sympress. By 2009, ten drugs were being developed with rozrolimupab (Sym001) being the lead product. Laboratoires Servier acquired Symphogen in 2020.

Cancer cell Tumor cell

Cancer cells are cells that divide relentlessly, forming solid tumors or flooding the blood with abnormal cells. Cell division is a normal process used by the body for growth and repair. A parent cell divides to form two daughter cells, and these daughter cells are used to build new tissue or to replace cells that have died because of aging or damage. Healthy cells stop dividing when there is no longer a need for more daughter cells, but cancer cells continue to produce copies. They are also able to spread from one part of the body to another in a process known as metastasis.

Immortalised cell line Lineage of cells that evades senescence and continues dividing

An immortalised cell line is a population of cells from a multicellular organism which would normally not proliferate indefinitely but, due to mutation, have evaded normal cellular senescence and instead can keep undergoing division. The cells can therefore be grown for prolonged periods in vitro. The mutations required for immortality can occur naturally or be intentionally induced for experimental purposes. Immortal cell lines are a very important tool for research into the biochemistry and cell biology of multicellular organisms. Immortalised cell lines have also found uses in biotechnology.

Immunology is the study of the immune system during health and disease. Below is a list of immunology-related articles.

HUMARA Assay is one of the most widely used methods to determine the clonal origin of a tumor. The method is based on X chromosome inactivation and it takes the advantage of having different methylation status of a gene called HUMARA that is located on X chromosome. Considering the fact that once one X chromosome is inactivated in a cell, all other cells derived from it will have the same X chromosome inactivated, this approach becomes a great tool to differentiate a monoclonal population from a polyclonal one in a female tissue. HUMARA gene, in particular, has three important features that make it highly convenient for the purpose.

Clonal hypereosinophilia, also termed primary hypereosinophilia or clonal eosinophilia, is a grouping of hematological disorders all of which are characterized by the development and growth of a pre-malignant or malignant population of eosinophils, a type of white blood cell that occupies the bone marrow, blood, and other tissues. This population consists of a clone of eosinophils, i.e. a group of genetically identical eosinophils derived from a sufficiently mutated ancestor cell.

Lymphocyte-variant hypereosinophila, is a rare disorder in which eosinophilia or hypereosinophilia is caused by an aberrant population of lymphocytes. These aberrant lymphocytes function abnormally by stimulating the proliferation and maturation of bone marrow eosinophil-precursor cells termed colony forming unit-Eosinophils or CFU-Eos.

References

  1. "Clone definition – Medical Dictionary definitions of popular medical terms easily defined on MedTerms". MedicineNet.com. 2013-08-28.
  2. "oligoclonal – Definition from Merriam-Webster's Medical Dictionary". Archived from the original on 2008-03-15. Retrieved 2008-05-05.
  3. Pozo-Garcia, Lucia; Diaz-Cano, Salvador J.; Taback, Bret; Hoon, Dave S.B. (January 2003). "Clonal origin and expansions in neoplasms: biologic and technical aspects must be considered together". The American Journal of Pathology. 162 (1): 353–355. doi: 10.1016/S0002-9440(10)63826-6 . PMC   1851102 . PMID   12507918.
  4. Parsons, Barbara L. (September 2008). "Many different tumor types have polyclonal tumor origin: evidence and implications". Mutation Research. 659 (3): 232–47. doi:10.1016/j.mrrev.2008.05.004. PMID   18614394.
  5. Comertpay, Sabahattin; Pastorino, Sandra; Tanji, Mika; Mezzapelle, Rosanna; Strianese, Oriana; et al. (4 December 2014). "Evaluation of clonal origin of malignant mesothelioma". Journal of Translational Medicine. 12 (1): 301. doi: 10.1186/s12967-014-0301-3 . PMC   4255423 . PMID   25471750.
  6. Bunn, Franklin; Wendell, Rosse (2005). Harrison's Principles of Internal Medicine. 1 (16th ed.). The McGraw-Hill Companies, Inc. p. 616. ISBN   0-07-144746-6.