INTRACELLULAR CD22 RAPIDLY MOVES TO THE CELL-SURFACE IN A TYROSINE KINASE-DEPENDENT MANNER FOLLOWING ANTIGEN RECEPTOR STIMULATION

CD22 is a key accessory molecule for Ag receptor signaling in 8 cells that becomes tyrosine phosphorylated ed in the signaling process, CD22 associates with sig and strongly amplifies sig-induced signals. Durin g B cell development, CD22 is initially expressed intracellularly, wit h surface expression appearing with IgD expression, We used confocal l aser-scanning microscopy and flow cytometry to analyze CD22 translocat ion responses to signaling events, Cross-linking surface IgM (sIgM) in duced rapid movement of CD22 to the cell surface in both Ramos and Dau di B cells, with a 50 to 100% increase in surface expression observed within 5 min of stimulation, The increase in CD22 surface expression w as specific in that CD19 expression was not affected. Both cell surfac e and intracellular CD22 were directed toward the site of sIgM stimula tion. Treatment with the phosphotyrosine phosphatase inhibitor bis(mal tolato)oxovanadium(IV) also increased CD22 surface expression, The tyr osine kinase inhibitor tyrphostin A10 inhibited CD22 movement at conce ntrations that inhibited tyrosine phosphorylation of CD22 and other ce llular proteins, In contrast to the B cell lines, mature peripheral bl ood B cells contained very little intracellular CD22 and showed no sig nificant increase in surface expression following sIgM stimulation. Th e rapid directed movement of intracellular CD22 provides a new mechani sm to dynamically regulate Ag receptor signaling, as well as CD22-medi ated adhesion.