B-lymphocyte antigen CD20 or CD20 is expressed on the surface of all
B-cells beginning at the pro-B phase (
CD45R+,
CD117+) and progressively increasing in concentration until maturity.[5]
This gene encodes a member of the
membrane-spanning 4A gene family. Members of this nascent protein family are characterized by common structural features and similar
intron/
exon splice boundaries and display unique expression patterns among
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
plasma cells. This family member is localized to 11q12, among a cluster of family members.
Alternative splicing of the human MS4A1 gene results in at least three transcript variants (1 to 3) that encode the same protein.[7] Variants 1 and 2 are poorly
translated due to inhibitory
upstream open reading frames and
stem-loop structures within their 5'
untranslated regions. The relative abundance of translation-competent variant 3, as opposed to the poorly translated variants 1 and 2, may be a key determinant of CD20 levels in normal and malignant human B cells and their responses to CD20-directed
immunotherapies. [8]
Function
The protein has no known natural
ligand[9] and its function is to enable optimal B-cell immune response, specifically against T-independent antigens.[10] It is suspected that it acts as a
calcium channel in the
cell membrane. CD20 is induced in the context of microenvironmental interactions by
CXCR4/SDF1 (
CXCL12) chemokine signaling and the molecular function of CD20 has been linked to the signaling propensity of
B-cell receptor (BCR) in this context.[11]
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
neoplasms, and is absent on otherwise similar appearing
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
Hodgkins disease,
myeloma, and
thymoma.[15]
Antibody FMC7 (Flinders Medical Centre) appears to recognise a conformational variant of CD20[16][17] also known as the FMC7 antigen.[18]
Although phase II trials for the use of
Rituximab in
myalgic encephalomyelitis showed promising results, these could not be replicated in a large randomized controlled trial [20] and preliminary results from a Phase III trial were negative.[21]
Additional anti-CD20 antibody therapeutics under development (phase II or III clinical trials in 2008) include :
A link between the
immune system's
B cells and
diabetes mellitus has been determined.[24] In cases of
obesity, the presence of fatty tissues surrounding the body's major organ systems results in cell
necrosis and insulin insensitivity 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
inflammation response that mobilizes both
T and
B cells results in the creation of
antibodies against these cells, causing them to become less responsive to
insulin by an as-yet-unknown mechanism and promoting
hypertension,
hypertriglyceridemia, and
arteriosclerosis, hallmarks of the
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 insensitivity 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 diabetes mellitus be reclassified as an
autoimmune disease rather than a purely metabolic one and focus treatment for it on immune system modulation.[25]
^"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^"Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^Hardy R (2008). "Chapter 7: B Lymphocyte Development and Biology". In Paul W (ed.). Fundamental Immunology (Book) (6th ed.). Philadelphia: Lippincott Williams & Wilkins. pp. 237–269.
ISBN978-0-7817-6519-0.
^Cragg MS, Walshe CA, Ivanov AO, Glennie MJ (2005). "The biology of CD20 and its potential as a target for mAb therapy". B Cell Trophic Factors and B Cell Antagonism in Autoimmune Disease. Current Directions in Autoimmunity. Vol. 8. pp. 140–74.
doi:
10.1159/000082102.
ISBN978-3-8055-7851-6.
PMID15564720.
^Cooper K, Anthony Leong AS-Y (2003). Manual of diagnostic antibodies for immunohistology (2nd ed.). London: Greenwich Medical Media.
ISBN978-1-84110-100-2.
^Serke S, Schwaner I, Yordanova M, Szczepek A, Huhn D (April 2001). "Monoclonal antibody FMC7 detects a conformational epitope on the CD20 molecule: evidence from phenotyping after rituxan therapy and transfectant cell analyses". Cytometry. 46 (2): 98–104.
doi:
10.1002/cyto.1071.
PMID11309819.
^"Diabetes Mellitus". The Lecturio Medical Concept Library. Retrieved 9 July 2021.
Further reading
Macardle PJ, Nicholson IC (2003). "CD20". Journal of Biological Regulators and Homeostatic Agents. 16 (2): 136–138.
PMID12144126.
Tamayose K, Sato N, Ando J, Sugimoto K, Oshimi K (December 2002). "CD3-negative, CD20-positive T-cell prolymphocytic leukemia: case report and review of the literature". American Journal of Hematology. 71 (4): 331–335.
doi:
10.1002/ajh.10224.
PMID12447967.
S2CID23999423.
Shirakawa T, Li A, Dubowitz M, Dekker JW, Shaw AE, Faux JA, et al. (June 1994). "Association between atopy and variants of the beta subunit of the high-affinity immunoglobulin E receptor". Nature Genetics. 7 (2): 125–129.
doi:
10.1038/ng0694-125.
PMID7920628.
S2CID24026689.
Maruyama K, Sugano S (January 1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1–2): 171–174.
doi:
10.1016/0378-1119(94)90802-8.
PMID8125298.
Szepetowski P, Perucca-Lostanlen D, Gaudray P (June 1993). "Mapping genes according to their amplification status in tumor cells: contribution to the map of 11q13". Genomics. 16 (3): 745–750.
doi:
10.1006/geno.1993.1257.
PMID8325649.
Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S (October 1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene. 200 (1–2): 149–156.
doi:
10.1016/S0378-1119(97)00411-3.
PMID9373149.