Monoclonal antibodies against HLA-DR antigens replace T helper cells in activation of B lymphocytes

Abstract

In the presence but not in the absence of pokeweed mitogen (PWM), monoclonal antibodies against HLA-DR antigens 147 and 164 helped highly purified B lymphocytes to proliferate and mature to Ig-secreting cells. In contrast, neither anti-DR antibody 231 nor the UCHTI monoclonal anti-human T cell antibody (both of the same isotype as the 147 and 164 anti-DR antibodies) exhibited any helper activity on B cells. B cells pulsed with PWM and subsequently cultured in the presence of anti-DR antibody 147 or 164 proliferated and secreted Ig, whereas B cells that first were pulsed with antibody 147 or 164 and then incubated with PWM did not. PWM alone did not induce any of these responses on purified B cells. Also, antibodies 147 and 164 significantly increased the number of Ig-secreting cells obtained from the WT51 Epstein-Barr virus-transformed B-cell line. Anti-DR antibody 231 inhibited the helper activity on WT51 cells mediated by anti-DR antibody 164. Finally, anti-DR antibodies 147 and 164 assisted B cells from the spleen of athymic nu/nu mice (which bear I-E-encoded products) to produce IgM antibodies against sheep erythrocytes. However, these antibodies had no effect on mouse B cells which do not express on their surface I-E-encoded Ia antigens. Taken collectively, these findings suggest that the structures detected by anti-DR antibodies 147 and 164 on B lymphocytes function as acceptors/transducers of T-cell-derived helper signals.