CD22, A B-LYMPHOCYTE-SPECIFIC ADHESION MOLECULE THAT REGULATES ANTIGEN RECEPTOR SIGNALING

The development of B lymphocytes is a highly regulated process that de pends in part on lineage-specific cell surface molecules. In addition, transmembrane signals generated through the B cell antigen receptor a nd other surface molecules regulate B cell responses to foreign antige ns. Recent studies reveal CD22 to be a functionally significant recept or during these processes. CD22 is first expressed in the cytoplasm of pro-B and pre-B cells, and on the surface as B cells mature to become IgD(+). CD22 is a member of the Ig superfamily that serves as an adhe sion receptor for sialic acid-bearing ligands expressed on erythrocyte s and all leukocyte classes. In addition to its potential role as a me diator of intercellular interactions, signal transduction through CD22 can activate B cells and modulate antigen receptor signaling in vitro . CD22 signaling is mediated via interactions with a number of kinases and phosphatases that bind the cytoplasmic domain through phosphoryla ted tyrosine residues located within consensus TAM and TIM motifs. The phenotype of CD22-deficient mice suggests that CD22 is primarily invo lved in the generation of mature B cells within the bone marrow, blood , and marginal zones of lymphoid tissues. Most notable in CD22-deficie nt mice is a significant diminution of surface Ig levels in these B ce ll subpopulations, which suggests that CD22 functions in vivo to adjus t the signaling threshold of cell surface antigen receptors. A further understanding of CD22 function is required and may reveal roles for C D22 in disease susceptibility or the development of autoimmunity.