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

Abstract

The injection of mice with 800 μg of an affinity‐purified goat antibody to mouse IgD (GaMδ) 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 GaMδ on all phases of B cell activation, as well as the effects of supplementing GaMG with varying quantities of normal goat IgG (GIgG). We have found that while 12.5 μg of GaMδ 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 μg of GaMδ is injected, while increases in B cell DNA synthesis usually require the injection of 200 μg of GaMδ and peak with doses of approximately 800 μg. Increases in splenic B cell number and DNA synthesis during the T‐dependent phase of GaMδ‐induced B cell activation are seen only in those mice that were injected with sufficient quantities of GaMδ to induce DNA synthesis during the T‐independent phase. Supplementing the dose of GaMδ injected with additional GIgG has no significant effect on B cell DNA synthesis or B cell number but dramatically increases polyclonal IgG_l secretion. Although mice which have been injected with 50 μg of GaMδ or with 800 pμ 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 μg of GaMδ plus 750 μg of GIgG. GIgG and larger doses of GaMδ similarly act synergistically to increase polyclonal IgG_l secretion. In contrast to the induction of polyclonal IgG_l secretion, the stimulation of polyclonal IgM secretion requires the injection of mitogenic doses of GaMδ 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 IgG_l secretion.