Regulation of MHC class II signal transduction by the B cell coreceptors CD19 and CD22

The major histocompatability class II heterodimer (class II) is expressed o n the surface of both resting and activated B cells. Although it is clear t hat class II expression is required for Ag presentation to CD4(+) T tells, substantial evidence suggests that class II serves as a signal transducing receptor that regulates B cell function. In ex vivo B cells primed by Ag re ceptor (BCR) crosslinking and incubation with IL-4, or B cell lines such as K46-17 mum lambda, class II ligation leads to the activation of protein ty rosine kinases, including Lyn and Syk and subsequent phospholipase C gamma -dependent mobilization of Ca2+. In this study, experiments demonstrated re ciprocal desensitization of class II and BCR signaling upon cross-linking o f either receptor, suggesting that the two receptors transduce signals via common processes and/or effector proteins. Because class II and BCR signal transduction pathways exhibit functional similarities, additional studies w ere conducted to evaluate whether class II signaling is regulated by BCR co receptors. Upon cross-linking of class II, the BCR coreceptors CD19 and CD2 2 were inducibly phosphorylated on tyrosine residues. Phosphorylation of CD 22 was associated with increased recruitment and binding of the protein tyr osine phosphatase SHP-1. Similarly, tyrosine phospharylation of CD19 result ed in recruitment and binding of Vav and phosphatidylinositol 3-kinase, Fin ally, co-cross-linking studies demonstrated that signaling via class II was either attenuated (CD22/SHP-1) or enhanced (CD19/ Vav and phosphatidylinos itol 3-kinase), depending on the coreceptor that was brought into close pro ximity, Collectively, these results suggest that CD19 and CD22 modulate cla ss II signaling in a manner similar to that for the BCR.