B-CELL ANTIGEN RECEPTOR-MEDIATED APOPTOSIS - IMPORTANCE OF ACCESSORY MOLECULES CD19 AND CD22, AND OF SURFACE IGM CROSS-LINKING

Engagement of the B cell Ag receptor can induce a suicide pathway in v arious B cell types. Earlier studies showed that anti-IgM mAb treatmen t triggers apoptotic death in the Burkitt lymphoma-derived cell line, Ramos. We show that two B cell surface molecules, CD19 and CD22, which have been reported to interact either functionally or structurally wi th the B cell Ag receptor, also stimulate cell suicide when sufficient ly aggregated, both in the Ramos and EBV-infected Ramos AW cell lines. In conditions of lower cross-linking, both molecules enhance the apop totic response induced by a suboptimal dose of anti-IgM mAb in Ramos c ells, reinforcing the nation that CD19 and CD22 may be involved in the death pathway and modulate Ag-induced B cell apoptosis. Similar outco mes were obtained with human tonsillar B cells, which enter the death program upon treatment with cross-linked anti-IgM, -CD19, or -CD22 mAb s. These results indicate that Ag-induced B cell suicide may affect ma ture B cells in the periphery and may be regulated via the interaction of CD19 and/or CD22 with their respective ligand(s). Early tyrosine p hosphorylations were analyzed by Western blotting. The biologic outcom e of these various treatments-cell survival or death-could not be rela ted to any detectable new tyrosine-phosphorylated substrate, further q uestioning the biochemical basis of apoptosis signaling.