Polyclonal activation of the murine immune system by an antibody to IgD. I. Increase in cell size and DNA synthesis
Finkelman, F.D.; Scher, I.; Mond, J.J.; Kung, J.T.; Metcalf, E.S.
Journal of Immunology 129(2): 629-637
1982
ISSN/ISBN: 0022-1767 PMID: 6177772 Document Number: 186429
The stimulation of B cell proliferation by a ligand-B lymphocyte surface Ig interaction has not been established in vivo. By 24 h after the injection of adult BALB/c mice with 800 .mu.g of an affinity-purified, isotype-specific goat antibody to mouse IgD (GaM.delta.), there was a substantial increase in size and DNA content of splenic B lymphocytes. Two days after GaM.delta. 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 GaM.delta. injection both B and T lymphocytes exhibited considerable increases in size and rate of DNA synthesis, and a 4- to 6-fold increase in spleen cell number was seen. In congenitally athymic (nu/nu) mice and mice tolerant to the injected anti-.delta. antibody only the early phase of B cell proliferation was seen. The interaction of a ligand with surface IgD appears to stimulate spleen cell proliferation in 2 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 Ig or a monoclonal rat antibody to a nonIg B lymphocyte surface molecule, ThB, did not stimulate B cell proliferation. The induction of B cell proliferation by anti-.delta. probably 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. The interaction of ligand with B cell surface Ig can have a physiologic role in the expansion of B cell clones that bind that ligand.