CD22 is a B lymphocyte-specific cell surface glycoprotein which belongs to the immunoglobulin gene superfamily and is highly homologous to numerous cell surface -adhesion molecules. Two independently expressed isoforms of CD22 have been identified and are structurally identical with the exception of two additional Ig-like extracellular domains which are present in the larger isoform, designated CD22beta, and absent from the smaller isoform, CD22alpha. The larger isoform, CD22beta, has been shown to bind T cells, B cells, monocytes and NK cells, and has been shown to bind to several alpha2,6-linked cell surface sialoglycoproteins. CD22beta appears to be involved in B cell interaction with virtually all leukocyte subsets and may clay an important role in the immune response. Most notably, CD22beta interacts with several isoforms of CD45 on T cells and soluble CD22 (CD22Rg) has been shown to modulate early signal transduction events during T cell activation through its direct interaction with CD45. This proposal aims at - elucidating the functional and physiologic role of CD22 during B cell activation as well as T cell-B cell interaction. The focus of this proposal will to be to determine the effect of CD22Rg binding to CD45 on early B cell activation events including calcium flux, phosphorylation of PLCgammal and inositol phosphate production. Additionally, a soluble CD45 chimera will be generated and used in assays to determine whether its binding to B cell CD22 represents a form of reciprocal communication during T cell-B cell interaction. Furthermore, B cells deficient in CD22 will be isolated and transfected with wild type or cytoplasmic deletion mutants to determine the role of the cytoplasmic domain of CD22 during B cell activation. Finally, because previous work has shown that CD22Rg can inhibit T cell activation in vivo, CD22Rg. will be used in in vitro - and in vivo models -of T cell-B cell cooperation and inflammatory disease to determine whether this molecule may be a useful tool to study lymphocyte function and whether it may provide a therapeutic reagent for modulation of autoimmune disorders.
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