Polyclonal activation of the murine immune system by an antibody to IgD. II. Generation of polyclonal antibody production and cells with surface IgG.

Abstract

Abstract In the accompanying paper we showed that the injection of BALB/c mice with 800 µg of GaMδ induced a direct polyclonal increase in B cell proliferation as well as an indirect increase in T cell proliferation. This led us to investigate whether the same treatment might lead to polyclonal Ig secretion. We found that 6 to 7 days after GaMδ injection one-quarter to one-half of splenic B lymphocytes lost detectable surface IgM and acquired surface IgG. Surface labeling experiments established that much of this IgG had the electrophoretic characteristics of membrane rather than serum IgG, and was, therefore intrinsic rather than cytophilic. GaMδ also induced a striking increase in Ig secretion 6 to 7 days after injection, as indicated by 1) an approximately eightfold increase in serum lgG1 levels and smaller increases in serum IgM and lgG2a levels; 2) greater than fivefold and 50-fold increases in the in vitro incorporation of 3H-leucine into IgM and IgG, respectively, by spleen cells from GaMδ-injected mice; and 3) three to 10-fold and 20 to 50-fold increases in the percentages of spleen cells with large amounts of intracytoplasmic IgM and IgG, respectively. The great majority of the increase in cell surface and secreted IgG was accounted for by an increase in the lgG1 subclass. Both absorption and plaquing studies indicated that the increase in Ig secretion was polyclonal rather than a specific immune response to goat Ig. The injection of anti-δ antibodies failed to induce B cells from congenitally athymic mice or mice that were tolerant to the injected anti-δ antibody to undergo a switch in cell surface isotype or to differentiate into antibody-secreting cells. We interpret these data and data presented in the companion paper as suggesting the binding to and cross-linking of B cell surface IgD by ligand leads to 1 ) direct activation of B lymphocytes that can include proliferation; 2) an indirect activation of T lymphocytes that can recognize the ligand as foreign; and 3) stimulation of activated B lymphocytes by T cell and/or accessory cell produced helper factors to undergo a switch in surface Ig isotype and to differentiate into antibody-secreting cells. The injection of mice with heat-aggregated goat IgG or a rat antibody to ThB failed to estimate a switch in surface Ig isotype or the differentiation of B cells into Ig-secreting cells. Thus, the anti-δ-induced events probably involve specific triggering of B cells by a surface lg-ligand interaction rather than simply the binding of ligand to the B cell. After the catabolism of injected GaMδ there is a rapid loss of surface lgG+ and lg-secreting cells that appears to be a consequence of cell death and that causes the spleen to return to a condition approximating its prestimulated state.