Polyclonal in vitro T cell proliferation and T cell-dependent B cell differentiation supported by activated...

Although anti-CD3-induced T cell proliferation and T cell-dependent B cell differentiation are not supported well by resting (nonactivated) B cells as AC, human peripheral blood B cells activated in vitro with SAC, rIL2, or anti-IgM effectively subserve AC function in a manner qualitatively similar to that of blood monocytes and support polyclonal anti-CD3-driven T cell-dependent B cell differentiation. Physical contact among T cells, responder B cells, and (irradiated) activated B cells is required, and the ability of activated B cells to support anti-CD3-driven generation of IgSC parallels surface B7 expression by the activated B cells. The fusion protein CTLA4Ig, which binds to B7 and B7-like molecules with high avidity and disrupts the interaction of T cell surface CD28 with B7, inhibits B cell differentiation in a dose-dependent fashion, whereas a control fusion protein has no such effect. Thus, activated B cells support polyclonal T cell-dependent B cell differentiation via a CD28 (CTLA4)/B7 (B7-like)-dependent mechanism.