B cell activation. V. Differentiation signaling of B cell membrane depolarization, increased I-A expression, G0 to G1 transition, and thymidine uptake by anti-IgM and anti-IgD antibodies.

Although studies have suggested that B cell membrane-associated IgM and IgD may function differently in the generation of humoral immune responses, this difference has proven difficult to define precisely. Toward a better understanding of the function of these antigen receptors, we compared the ability of F(ab')2 fragments of antibodies specific for mouse Fab, IgM, and IgD to induce early changes in B cell physiology that are indicative of cell activation. Specifically, we assessed the ability of membrane IgM (mIgM) or membrane IgD (mIgD) or both in combination to transduce signals that result in membrane depolarization, increased I-A expression, G0 to G1 transition, and thymidine uptake. Results indicate that at low levels of anti-receptor antibody (0.01 to 0.1 microgram/ml) both isotypes transduce signals for the induction of membrane depolarization and increased I-A expression by a significant proportion of B cells, i.e., Ig+ cells. Higher concentrations of ligand (5 to 25 micrograms/ml) are required to induce a significant proportion of cells to undergo G0 to G1 transition and increase thymidine uptake. At optimal concentrations, anti-IgM and anti-IgD induce membrane depolarization and increased I-A expression by 80 to 90% of B cells. Although mIgM also transduces signals sufficient for G0 to G1 transition by 80 to 90% of B cells, mIgD transduces signals sufficient for G0 to G1 by only about 40% of B cells. A similar difference exists for the induction of thymidine uptake. Thus, results suggest that membrane Ig may transduce two different signals depending upon the amount of ligand that they bind. Although in some B cells mIgD can transduce both signals resulting in membrane depolarization and progression into G1, in most cells mIgD transduces only the first signal, resulting in membrane depolarization and increased I-A expression.