Abortive activation of B lymphocytes by monoclonal anti-immunoglobulin antibodies.

Abstract

Toward a better understanding of the signaling role of antigen-mIg binding in the generation of humoral immune responses, we have assessed the effects of soluble, monoclonal anti-Ig antibodies on various cell physiologic parameters known to change during B cell activation. These parameters include membrane potential, I-A antigen expression, narrow angle light scattering properties (size), and cell cycle state. Results indicate that all monoclonal antibodies that bind cell to surface IgM or IgD, or both, induce virtually all small B cells to undergo membrane depolarization and increased I-A expression. Only a small subset of these antibodies, exemplified by b-7-6 anti-mu, induce all small B cells to enter G1. An increasingly smaller proportion of these cells traverse each subsequent cell cycle phase, with 10% of cells reaching G2 or M phases by 60 hr of culture. The kinetics of this response to b-7-6 are considerably slower than those of the response induced by LPS. Finally, analysis of Percoll density-fractionated cells revealed that although B blasts made by b-7-6 stimulation of small cells remain b-7-6 responsive, natural B blasts isolated from the spleen are refractory to monoclonal anti-Ig stimulation as indicated by membrane depolarization, increased IA expression, blastogenesis, and [3H]thymidine uptake.