Cross-linking of B lymphocyte Fcγ receptors and membrane immunoglobulin inhibits anti-immunoglobulin-induced blastogenesis

The Fc portion of rabbit anti-mouse immunoglobulin (Ig) antibodies interferes with anti-Ig-induced B lymphocyte activation as measured by DNA synthesis on day 3 of culture or maturation to Ig-secreting cells in the presence of soluble helper factors on day 4 or 5. To investigate this Fc-dependent effect at an earlier stage in B cell activation, rabbit IgG anti-mouse μ-chain- or δ-chain-specific antibodies were compared with their F(ab')₂ fragments for the ability to induce mouse B cells to undergo blast transformation, as defined by a increase in cell volume during the first 24 hr of culture. Both F(ab')₂ anti-Ig reagents induce blast transformation, although F(ab')₂ anti-μ antibodies induce a greater size change than F(ab')₂ anti-δ antibodies. Whole anti-μ or anti-δ antibodies do not induce blast transformation; however, in the presence of a monoclonal anti-mouse Fcγ receptor antibody that blocks IgG binding to Fcγ receptors (FcγR), whole anti-μ or anti-δ antibodies induce blast transformation as well as their F(ab')₂ fragments. Because the anti-FcγR antibody alone has no effect on blast transformation, it appears that the simultaneous binding of membrane IgM (or IgD) and FcγR by whole anti-Ig antibodies prevent this early event in membrane Ig-induced B cell activation.