CD20

B-lymphocyte antigen CD20 or CD20 is an activated-is_associated_with::glycosylated is_associated_with::phosphoprotein expressed on the surface of all is_associated_with::B-cells beginning at the pro-B phase (is_associated_with::CD45R+, is_associated_with::CD117+) and progressively increasing in concentration until maturity.

In humans CD20 is encoded by the MS4A1 is_associated_with::gene.

This gene encodes a member of the is_associated_with::membrane-spanning 4A gene family. Members of this nascent protein family are characterized by common structural features and similar is_associated_with::intron/is_associated_with::exon splice boundaries and display unique expression patterns among is_associated_with::hematopoietic cells and nonlymphoid tissues. This gene encodes a B-lymphocyte surface molecule that plays a role in the development and differentiation of B-cells into is_associated_with::plasma cells. This family member is localized to 11q12, among a cluster of family members. Alternative splicing of this gene results in two transcript variants that encode the same protein.

Function
The protein has no known natural is_associated_with::ligand and its function is to enable optimal B-cell immune response, specifically against T-independent antigens. It is suspected that it acts as a is_associated_with::calcium channel in the is_associated_with::cell membrane.

Expression
CD20 is expressed on all stages of B cell development except the first and last; it is present from is_associated_with::late pro-B cells through memory cells, but not on either early pro-B cells or plasma blasts and is_associated_with::plasma cells. It is found on B-cell is_associated_with::lymphomas, is_associated_with::hairy cell leukemia, B-cell is_associated_with::chronic lymphocytic leukemia, and melanoma is_associated_with::cancer stem cells.

is_associated_with::Immunohistochemistry can be used to determine the presence of CD20 on cells in histological tissue sections. Because CD20 remains present on the cells of most B-cell is_associated_with::neoplasms, and is absent on otherwise similar appearing is_associated_with::T-cell neoplasms, it can be very useful in diagnosing conditions such as B-cell lymphomas and leukaemias. However, the presence or absence of CD20 in such tumours is not relevant to prognosis, with the progression of the disease being much the same in either case. CD20 positive cells are also sometimes found in cases of is_associated_with::Hodgkins disease, is_associated_with::myeloma, and is_associated_with::thymoma.

Antibody FMC7 appears to recognise a conformational variant of CD20 also known as the FMC7 antigen.

Clinical significance
CD20 is the target of the is_associated_with::monoclonal antibodies (mAb) is_associated_with::rituximab, is_associated_with::obinutuzumab, is_associated_with::Ibritumomab tiuxetan, and is_associated_with::tositumomab, which are all active agents in the treatment of all B cell is_associated_with::lymphomas and is_associated_with::leukemias. The anti-CD20 mAB is_associated_with::Ofatumumab (is_associated_with::Genmab) was approved by FDA in Oct 2009 for is_associated_with::Chronic lymphocytic leukemia.

The anti-CD20 mAB is_associated_with::obinutuzumab (Gazyva) was approved by FDA in November 2013 for is_associated_with::Chronic lymphocytic leukemia.

Additional anti-CD20 antibody therapeutics under development (phase II or III clinical trials in 2008) include :
 * AME-133v (by Applied Molecular Evolution),
 * is_associated_with::Ocrelizumab for is_associated_with::multiple sclerosis (is_associated_with::rheumatoid arthritis discontinued in 2010),
 * TRU-015 (by is_associated_with::Trubion), (discontinued in 2010 )
 * IMMU-106 (is_associated_with::veltuzumab).

B cells, CD20, and diabetes mellitus
A link between the is_associated_with::immune system's is_associated_with::B cells and is_associated_with::diabetes mellitus has been determined. In cases of is_associated_with::obesity, the presence of fatty tissues surrounding the body's major organ systems results in cell is_associated_with::necrosis and insulin desensitivity along the boundary between them. Eventually, the contents of fat cells that would otherwise have been digested by insulin are shed into the bloodstream. An is_associated_with::inflammation response that mobilizes both T and is_associated_with::B cells results in the creation of is_associated_with::antibodies against these cells, causing them to become less responsive to is_associated_with::insulin by an as-yet unknown mechanism and promoting is_associated_with::hypertension, is_associated_with::hypertriglyceridemia, and is_associated_with::arteriosclerosis, hallmarks of the is_associated_with::metabolic syndrome. Obese mice administered anti-B cell CD-20 antibodies, however, did not become less responsive to insulin and as a result did not develop diabetes mellitus or the metabolic syndrome, the posited mechanism being that anti-CD20 antibodies rendered the T cell antibodies dysfunctional and therefore powerless to cause insulin desensitivity by a B cell antibody-modulated autoimmune response. The protection afforded by anti-CD-20 lasted approximately forty days—the time it takes the body to replenish its supply of B cells—after which repetition was necessary to restore it. Hence it has been argued that obesity be reclassified as an is_associated_with::autoimmune disease rather than a purely metabolic one and focus treatment for it on immune system modulation.