Polyclonal activation of the murine immune system by an antibody to IgD. I. Increase in cell size and DNA synthesis.

Abstract

Abstract Although anti-immunoglobulin antibodies induce B lymphocyte proliferation in some in vitro culture systems, the stimulation of B cell proliferation by a ligand-B lymphocyte surface immunoglobulin interaction has not been established in vivo. We found that by 24 hr after the injection of adult BALB/c mice with 800 µg of an affinity-purified, isotype-specific goat antibody to mouse IgD (GaMδ) there was a substantial increase in size and DNA content of splenic B lymphocytes. Two days after GaMδ injection almost all splenic B cells had increased in size, and these cells exhibited a several fold increase in the rate of DNA synthesis. Although there was no increase in the size or extent of proliferation of T lymphocytes at this time, by 7 days after GaMδ injection both B and T lymphocytes exhibited considerable increases in size and rate of DNA synthesis, and a four to sixfold increase in spleen cell number was seen. In congenitally athymic (nu/nu) mice and mice tolerant to the injected anti-δ antibody only the early phase of B cell proliferation was seen. Thus, the interaction of a ligand with surface IgD appears to stimulate spleen cell proliferation in two phases; an early, T-independent, carrier-independent phase that involves B cells but not T cells, and a later T-dependent, carrier-dependent phase that involves both sets of lymphocytes. The injection of mice with heat-aggregated goat immunoglobulin or a monoclonal rat antibody to a nonimmunoglobulin B lymphocyte surface molecule, ThB, did not stimulate B cell proliferation. This suggests that the induction of B cell proliferation by anti-δ results from a specific signal generated by the binding to and cross-linking of surface IgD by ligand, rather than by the binding of ligand to any B cell surface molecule. These results indicate that the interaction of ligand with B cell surface immunoglobulin can have a physiologic role in the expansion of B cell clones that bind that ligand.