Polyclonal activation of the murine immune system by an antibody to IgD. VI. Influence of doses of goat anti-mouse delta chain and normal goat IgG on B lymphocyte proliferation and differentiation.

The injection of mice with 800 micrograms of an affinity-purified goat antibody to mouse IgD (GaM delta) induces early, T-independent polyclonal increases in the expression of B cell surface Ia, and B cell size and DNA synthesis, as well as later, T-dependent polyclonal increases in spleen cell number and Ig secretion. We have now studied the effects of varying the doses of injected GaM delta on all phases of B cell activation, as well as the effects of supplementing GaM delta with varying quantities of normal goat IgG (GIgG). We have found that while 12.5 micrograms of GaM delta modulates most of the IgD from the surface of splenic B lymphocytes, it fails to activate these cells. Increases in the expression of B cell surface Ia are first seen when 50 micrograms of GaM delta is injected, while increases in B cell DNA synthesis usually require the injection of 200 micrograms of GaM delta and peak with doses of approximately 800 micrograms. Increases in splenic B cell number and DNA synthesis during the T-dependent phase of GaM delta-induced B cell activation are seen only in those mice that were injected with sufficient quantities of GaM delta to induce DNA synthesis during the T-independent phase. Supplementing the dose of GaM delta injected with additional GIgG has no significant effect on B cell DNA synthesis or B cell number but dramatically increases polyclonal IgG1 secretion. Although mice which have been injected with 50 micrograms of GaM delta or with 800 micrograms of GIgG alone have few polyclonal IgG1-secreting cells, substantial increases in the number of IgG1-secreting cells are seen in mice injected with 50 micrograms of GaM delta plus 750 micrograms of GIgG. GIgG and larger doses of GaM delta similarly act synergistically to increase polyclonal IgG1 secretion. In contrast to the induction of polyclonal IgG1 secretion, the stimulation of polyclonal IgM secretion requires the injection of mitogenic doses of GaM delta and is not enhanced by the injection of additional GIgG. These observations suggest that, in this model system, stimulatory signals that activate B cells through their surface Ig are limiting for the induction of polyclonal proliferation and IgM secretion, while the generation of T helper lymphokines that do not directly interact with B cells through their surface Ig may be more limiting for the stimulation of polyclonal IgG1 secretion.