MEMBRANE IGM-INDUCED TYROSINE PHOSPHORYLATION OF CD19 REQUIRES A CD19DOMAIN THAT MEDIATES ASSOCIATION WITH COMPONENTS OF THE B-CELL ANTIGEN RECEPTOR COMPLEX

CD19 enhances membrane IgM (mIgM) signaling and is required for B lymp hocyte responses to T-dependent Ags, CD19 is tyrosine phosphorylated w hen mIgM is ligated and binds SH2 domain-containing signaling proteins , We suggest that the basis for phosphorylation is the association of CD19 with Syk and other components of the mIgM complex, IgM, CD22, Ig- alpha, Ig-beta, and Syk were coimmunoprecipitated with CD19 from deter gent lysates of B lymphocytes. The association was maintained with a c himeric form of CD19 containing only the transmembrane domain and the membrane proximal 17 amino acids of the cytoplasmic domain encoded by exon 6. This sequence is sufficient to mediate the association, as a s ynthetic peptide of the exon 6-encoded region adsorbs IgM and Syk, Del etion of the juxtamembrane 17 amino acids of the cytoplasmic domain en coded by CD19 exon 6 abolishes association of CD19 with the mIgM compl ex. Deletion of these amino acids, which contain no tyrosines, also re duces mIgM-induced tyrosine phosphorylation of the remainder of the CD 19 cytoplasmic domain, Coligating this mutant CD19 to mIgM restores ph osphorylation. Thus, a discrete region of the cytoplasmic domain regul ates the tyrosine phosphorylation of CD19 in the activation of B cells by mIgM.