CD22 , or CD22 B-cell receptor, is a B-lymphocyte membrane receptor protein that is encoded in humans by the CD22 gene . CD22 is synthesized by B cells, starting from the pro-B cell stage, at this stage the protein is in the cytoplasm . At the stage of pre-B cells, CD22 moves into the cell membrane and remains on the surface of activated B cells and memory B cells, disappearing only in plasma cells . CD22 is an inhibitory co-receptor of the B-cell receptor : it lowers its sensitivity and prevents overstimulation of the cell with antigen [1] . This receptor is a target for some drugs against malignant blood diseases , which are currently undergoing clinical trials [2] .
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CD22 mRNA encodes a polypeptide with a length of 847 amino acid residues . A mature protein has a molecular weight of about 140 kDa and contains 7 immunoglobulin-like domains .
Signal Transmission
In the cell membrane, CD22 is in contact with the B-cell receptor and regulates its activity. After stimulation of the B-cell receptor with the tyrosine kinase antigen, Lyn phosphorylates tyrosine residues in the cytoplasmic tail of CD22. Tyrosine phosphatase SHP-1, containing the SH2 domain, binds to phosphorylated CD22. This phosphatase dephosphorylates (that is, deactivates) many molecules involved in signal transduction from the B-cell receptor, for example, Vav-1, CD19, and SLP65 [1] .
CD22 inhibits Ca 2+ -dependent signal transmission from the B-cell receptor. This is due, firstly, to the fact that CD22 deactivates (with the participation of SHP-1) the Vav1, CD19, and SLP65 proteins, which are components of the signal chain leading to the release of intracellular calcium ions from their storage sites. In addition, phosphorylated CD22 in combination with SHP-1 binds and activates the PMCA-4 membrane pump ( English plasma membrane Ca 2+ ATPase-4 ), which pumps calcium ions from the cytoplasm of the cell, thereby stopping the signal transmission by this secondary messenger [1 ] .
Role in the development of B-lymphocytes
The role of CD22 in the fate of B-lymphocytes was investigated using mice in which this gene was artificially inactivated. B-lymphopoiesis proceeds normally in such mice [3] [4] [5] [6] . The number of mature recirculating B-lymphocytes is normal, but their lifespan and bone marrow content are reduced. In two of four studies, an increase in the B1 lymphocyte population was found. Mature B-lymphocytes of CD22 - / - mice are hyperreactive: to stimulate them, a lower concentration of antigen is required than to stimulate normal B-lymphocytes. In addition, an impaired immune response to thymus-independent antigens was observed in animals.
Notes
- ↑ 1 2 3 Nitschke L. CD22 and Siglec-G: B-cell inhibitory receptors with distinct functions // Immunol Rev. - 2009. - T. 230 , no. 1 . - S. 128-143 . - DOI : 10.1111 / j.1600-065X.2009.00801.x . - PMID 19594633 .
- ↑ Leonard JP, Coleman M., Ketas JC, Chadburn A., Furman R., Schuster MW, Feldman EJ, Ashe M., Schuster SJ, Wegener WA, Hansen HJ, Ziccardi H., Eschenberg M., Gayko U., Fields SZ, Cesano A., Goldenberg DM Epratuzumab, a humanized anti-CD22 antibody, in aggressive non-Hodgkin's lymphoma: phase I / II clinical trial results // Clin Cancer Res. - 2004. - T. 10 , no. 16 . - S. 5327-5334 . - PMID 15328168 .
- ↑ Otipoby KL, Andersson KB, Draves KE, Klaus SJ, Farr AG, Kerner JD, Perlmutter RM, Law CL, Clark EA CD22 regulates thymus-independent responses and the lifespan of B cells // Nature. - 1996. - T. 384 , no. 6610 - S. 634-637 . - PMID 8967951 .
- ↑ O'Keefe TL, Williams GT, Davies SL, Neuberger MS Hyperresponsive B cells in CD22-deficient mice // Science. - 1996. - T. 274 , no. 5288 . - S. 798-801 . - PMID 8864124 .
- ↑ Sato S., Miller AS, Inaoki M., Bock CB, Jansen PJ, Tang ML, Tedder TF CD22 is both a positive and negative regulator of B lymphocyte antigen receptor signal transduction: altered signaling in CD22-deficient mice // Immunity. - 1996. - T. 5 , no. 6 . - S. 551-562 . - PMID 8986715 .
- ↑ Nitschke L., Carsetti R., Ocker B., Köhler G., Lamers MC CD22 is a negative regulator of B-cell receptor signaling // Curr Biol. - 1997. - T. 7 , no. 2 . - S. 133-143 . - PMID 9016707 .