CD37 explained

Leukocyte antigen CD37 is a protein that in humans is encoded by the CD37 gene.^{[1] [2]}

Function

The protein encoded by this gene is a member of the transmembrane 4 superfamily, also known as the tetraspanin family. Most of these members are cell-surface proteins that are characterized by the presence of four hydrophobic transmembrane domains. Tetraspanins mediate signal transduction events that play a role in the regulation of immune responses, cell development, activation, growth and motility.^{[3] [4] [5] [6]} CD37 expression is restricted to cells of the immune system, with highest abundance on mature B cells, and lower expression is found on T cells and myeloid cells. CD37 is a cell surface glycoprotein that is known to complex with integrins and other transmembrane 4 superfamily proteins. Alternate splicing results in multiple transcript variants encoding different isoforms. CD37 controls both humoral^{[7] [8]} and cellular immune responses.^{[9] [10] [11]} CD37-deficiency in mice leads to spontaneous development on B cell lymphoma,^[12] and patients with CD37-negative lymphomas have a worse clinical outcome.^[13]

See also

• Cluster of differentiation

Further reading

• Horejsí V, Vlcek C . Novel structurally distinct family of leucocyte surface glycoproteins including CD9, CD37, CD53 and CD63 . FEBS Letters . 288 . 1–2 . 1–4 . August 1991 . 1879540 . 10.1016/0014-5793(91)80988-F . 26316623 .
• Berditchevski F . Complexes of tetraspanins with integrins: more than meets the eye . Journal of Cell Science . 114 . Pt 23 . 4143–51 . December 2001 . 10.1242/jcs.114.23.4143 . 11739647 .
• Classon BJ, Williams AF, Willis AC, Seed B, Stamenkovic I . The primary structure of the human leukocyte antigen CD37, a species homologue of the rat MRC OX-44 antigen . The Journal of Experimental Medicine . 172 . 3 . 1007 . September 1990 . 2388030 . 2188538 . 10.1084/jem.172.3.1007 .
• Classon BJ, Williams AF, Willis AC, Seed B, Stamenkovic I . The primary structure of the human leukocyte antigen CD37, a species homologue of the rat MRC OX-44 antigen . The Journal of Experimental Medicine . 169 . 4 . 1497–502 . April 1989 . 2466944 . 2189247 . 10.1084/jem.169.4.1497 .
• Schwartz-Albiez R, Dörken B, Hofmann W, Moldenhauer G . The B cell-associated CD37 antigen (gp40-52). Structure and subcellular expression of an extensively glycosylated glycoprotein . Journal of Immunology . 140 . 3 . 905–14 . February 1988 . 10.4049/jimmunol.140.3.905 . 3257508 . 23948434 . free .
• Angelisová P, Hilgert I, Horejsí V . Association of four antigens of the tetraspans family (CD37, CD53, TAPA-1, and R2/C33) with MHC class II glycoproteins . Immunogenetics . 39 . 4 . 249–56 . 1994 . 8119731 . 10.1007/BF00188787 . 20252327 .
• Wright MD, Rochelle JM, Tomlinson MG, Seldin MF, Williams AF . Gene structure, chromosomal localization, and protein sequence of mouse CD53 (Cd53): evidence that the transmembrane 4 superfamily arose by gene duplication . . 5 . 2 . 209–16 . February 1993 . 8452817 . 10.1093/intimm/5.2.209 .
• Serru V, Le Naour F, Billard M, Azorsa DO, Lanza F, Boucheix C, Rubinstein E . Selective tetraspan-integrin complexes (CD81/alpha4beta1, CD151/alpha3beta1, CD151/alpha6beta1) under conditions disrupting tetraspan interactions . The Biochemical Journal . 340 . 1 . 103–11 . May 1999 . 10229664 . 1220227 . 10.1042/0264-6021:3400103 .
• Okochi H, Mine T, Nashiro K, Suzuki J, Fujita T, Furue M . Expression of tetraspans transmembrane family in the epithelium of the gastrointestinal tract . Journal of Clinical Gastroenterology . 29 . 1 . 63–7 . July 1999 . 10405235 . 10.1097/00004836-199907000-00016 .
• Matsumoto K, Bochner BS, Wakiguchi H, Kurashige T . Functional expression of transmembrane 4 superfamily molecules on human eosinophils . International Archives of Allergy and Immunology . 120 . 38–44 . 1999 . Suppl 1 . 10529602 . 10.1159/000053592 . 39289159 .
• van Spriel AB, Puls KL, Sofi M, Pouniotis D, Hochrein H, Orinska Z, Knobeloch KP, Plebanski M, Wright MD . A regulatory role for CD37 in T cell proliferation . Journal of Immunology . 172 . 5 . 2953–61 . March 2004 . 14978098 . 10.4049/jimmunol.172.5.2953 . 5620186 .
• Suzuki Y, Yamashita R, Shirota M, Sakakibara Y, Chiba J, Mizushima-Sugano J, Nakai K, Sugano S . Sequence comparison of human and mouse genes reveals a homologous block structure in the promoter regions . Genome Research . 14 . 9 . 1711–8 . September 2004 . 15342556 . 515316 . 10.1101/gr.2435604 .
• Meyer-Wentrup F, Figdor CG, Ansems M, Brossart P, Wright MD, Adema GJ, van Spriel AB . Dectin-1 interaction with tetraspanin CD37 inhibits IL-6 production . Journal of Immunology . 178 . 1 . 154–62 . January 2007 . 17182550 . 10.4049/jimmunol.178.1.154 . free .
• Zhao X, Lapalombella R, Joshi T, Cheney C, Gowda A, Hayden-Ledbetter MS, Baum PR, Lin TS, Jarjoura D, Lehman A, Kussewitt D, Lee RJ, Caligiuri MA, Tridandapani S, Muthusamy N, Byrd JC . Targeting CD37-positive lymphoid malignancies with a novel engineered small modular immunopharmaceutical . Blood . 110 . 7 . 2569–77 . October 2007 . 17440052 . 1988922 . 10.1182/blood-2006-12-062927 .

Notes and References

1. Virtaneva KI, Angelisová P, Baumruker T, Horejsí V, Nevanlinna H, Schröder J . The genes for CD37, CD53, and R2, all members of a novel gene family, are located on different chromosomes . Immunogenetics . 37 . 6 . 461–5 . Mar 1993 . 8436422 . 10.1007/BF00222471 . 10138/157839 . 8899453 . free .
2. Web site: Entrez Gene: CD37 CD37 molecule.
3. Levy S, Shoham T . The tetraspanin web modulates immune-signalling complexes . Nature Reviews. Immunology . 5 . 2 . 136–48 . February 2005 . 15688041 . 10.1038/nri1548 . 1756810 .
4. Charrin S, le Naour F, Silvie O, Milhiet PE, Boucheix C, Rubinstein E . Lateral organization of membrane proteins: tetraspanins spin their web . The Biochemical Journal . 420 . 2 . 133–54 . May 2009 . 19426143 . 10.1042/BJ20082422 .
5. Hemler ME . Tetraspanin functions and associated microdomains . Nature Reviews Molecular Cell Biology . 6 . 10 . 801–11 . October 2005 . 16314869 . 10.1038/nrm1736 . 5906694 .
6. van Deventer SJ, Dunlock VE, van Spriel AB. Molecular interactions shaping the tetraspanin web . Biochemical Society Transactions . 45 . 3 . 741–750 . 2017-06-15 . 28620035 . 10.1042/BST20160284 . free .
7. van Spriel AB, Sofi M, Gartlan KH, van der Schaaf A, Verschueren I, Torensma R, Raymakers RA, Loveland BE, Netea MG, Adema GJ, Wright MD, Figdor CG . The tetraspanin protein CD37 regulates IgA responses and anti-fungal immunity . PLOS Pathogens . 5 . 3 . e1000338 . March 2009 . 19282981 . 2650281 . 10.1371/journal.ppat.1000338 . free .
8. van Spriel AB, de Keijzer S, van der Schaaf A, Gartlan KH, Sofi M, Light A, Linssen PC, Boezeman JB, Zuidscherwoude M, Reinieren-Beeren I, Cambi A, Mackay F, Tarlinton DM, Figdor CG, Wright MD . The tetraspanin CD37 orchestrates the α(4)β(1) integrin-Akt signaling axis and supports long-lived plasma cell survival . Science Signaling . 5 . 250 . ra82 . November 2012 . 23150881 . 10.1126/scisignal.2003113 . 21237789 .
9. Knobeloch KP, Wright MD, Ochsenbein AF, Liesenfeld O, Löhler J, Zinkernagel RM, Horak I, Orinska Z . Targeted inactivation of the tetraspanin CD37 impairs T-cell-dependent B-cell response under suboptimal costimulatory conditions . Molecular and Cellular Biology . 20 . 15 . 5363–9 . August 2000 . 10891477 . 10.1128/MCB.20.15.5363-5369.2000 . 85988.
10. van Spriel AB, Puls KL, Sofi M, Pouniotis D, Hochrein H, Orinska Z, Knobeloch KP, Plebanski M, Wright MD . A regulatory role for CD37 in T cell proliferation . Journal of Immunology . 172 . 5 . 2953–61 . March 2004 . 14978098 . 10.4049/jimmunol.172.5.2953 . 5620186 .
11. Sheng KC, van Spriel AB, Gartlan KH, Sofi M, Apostolopoulos V, Ashman L, Wright MD . Tetraspanins CD37 and CD151 differentially regulate Ag presentation and T-cell co-stimulation by DC . European Journal of Immunology . 39 . 1 . 50–5 . January 2009 . 19089816 . 10.1002/eji.200838798 . 46297687 .
12. de Winde CM, Veenbergen S, Young KH, Xu-Monette ZY, Wang XX, Xia Y, Jabbar KJ, van den Brand M, van der Schaaf A, Elfrink S, van Houdt IS, Gijbels MJ, van de Loo FA, Bennink MB, Hebeda KM, Groenen PJ, van Krieken JH, Figdor CG, van Spriel AB . Tetraspanin CD37 protects against the development of B cell lymphoma . The Journal of Clinical Investigation . 126 . 2 . 653–66 . February 2016 . 26784544 . 4731177 . 10.1172/JCI81041 .
13. Xu-Monette ZY, Li L, Byrd JC, Jabbar KJ, Manyam GC, Maria de Winde C, van den Brand M, Tzankov A, Visco C, Wang J, Dybkaer K, Chiu A, Orazi A, Zu Y, Bhagat G, Richards KL, Hsi ED, Choi WW, Huh J, Ponzoni M, Ferreri AJ, Møller MB, Parsons BM, Winter JN, Wang M, Hagemeister FB, Piris MA, Han van Krieken J, Medeiros LJ, Li Y, van Spriel AB, Young KH . Assessment of CD37 B-cell antigen and cell of origin significantly improves risk prediction in diffuse large B-cell lymphoma . Blood . 128 . 26 . 3083–3100 . December 2016 . 27760757 . 5201094 . 10.1182/blood-2016-05-715094 .