B cells in autoimmune (NZB x NZW)F1 mice show altered IgG isotype switching upon T cell-dependent antigenic stimulation in vitro.

Humoral immune responses of (NZB x NZW)F1 (BWF1) autoimmune mice to T cell-dependent antigens often exhibit a predominance of IgG2 antibodies, while normal mice produce IgG1 antibodies. In order to determine whether this results from differences in properties of the B cells or the T cells involved, the responses of both primary and secondary BWF1 B cells to the antigen DNP-hemocyanin (Hy) were measured in limiting dilution splenic fragment cultures in the presence of normal T cell help. Furthermore, the capacity of Hy-primed lymph node T cells from BWF1 mice to provide help to BALB/c nu/nu B cells was determined in modified splenic fragment cultures. These experiments indicated that (a) stimulation of primary BWF1 B cells with DNP-Hy and normal T cell help failed to yield significant numbers of clones which produced any of the IgG isotypes; (b) antigenic stimulation of BWF1 secondary B cell clones also demonstrated a paucity of IgG1, but elevated production of IgG2 isotypes; and (c) Hy-primed BWF1 lymph node T cells were comparable to those derived from BALB/c mice in their capacity to provide both help for nu/nu B cell responses and modulation of IgG isotype switching. BWF1 B cells apparently differ from normal murine B cells in their capacity to produce IgG antibodies upon T cell-dependent antigenic stimulation.