T cell regulation of isotype expression. The requirement for a second Ig-specific helper T cell population for the induction of IgG responses.

A characteristic of the in vivo responses to T-dependent antigens is the highly restricted expression of Ig heavy chain classes of both the antibody and nonspecific Ig produced. To investigate the cellular interactions which regulate expression of Ig class, sheep red blood cell- and keyhole limpet hemocyanin-primed BALB/c T cells were tested in vitro for their ability to induce normal BALB/c B cells to selective Ig secretion. The results, based initially on linear regression analysis, indicate that while the production of IgM required help from a single antigen-specific helper cell, additional signals from a second pool of helper cells were necessary for the expression of IgG isotypes. The greatly diminished ability of primed T cells from mice suppressed from birth for IgM production to induce IgG responses indicated that the generation of this second class-regulating T cell pool requires the presence of Ig, probably B cell-presented, during the period of priming. Bases on the present data, secretion of IgG by normal B cells can be explained by invoking the requirement for a second pool of helper T cells which recognize Ig determinant, in contrast to the I region recognition known to exist for effective help by the first helper cell. In addition, it is proposed that in the absence of such a second signal only IgM secretion will occur.