T cell regulation of immunoglobulin class expression in the antibody response to trinitrophenyl-ficoll. Evidence for T cell enhancement of the immunoglobulin class switch.

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Abstract
In the absence of T cells, [mouse] B cells responded to the type 2 T-independent (TI-2) antigen, trinitrophenyl (TNP)-Ficoll, with a characteristic hierarchy of IgM and IgG subclass antibody (Ab) production; this directly correlated with 5'' to 3'' Igh-C gene order, i.e., IgM > IgG3 > IgG1 > IgG2b > IgG-2a. This was evident when immune serum Ab titers were analyzed, when in vitro secretion of Ab from immune cells was measured and when TNP-Ficoll-stimulated clones in a splenic focus assay were analyzed for isotype production. T cells caused a preferential relative increase in the amount of IgG2a Ab produced to TNP-Ficoll. The T cell responsible was present in anti-IgM neonatally-suppressed mice and was needed early in the response, i.e., on the day of immunization or earlier. T cells increased the frequency of TNP-Ficoll-responsive B cell clones that produced IgG2a in the splenic focus assay. The great majority of these IgG2a-positive clones also produced IgM and all or nearly all of the IgG isotypes in which genes are encoded 5'' to the Igh-.gamma.2a gene. T cell enhancement of IgG2a Ab synthesis appears to be mediated through T cell enhancement of the Igh-C gene switching mechanism within TNP-Ficoll-responsive B cell clones. Thus, isotypes encoded by genes on the 3'' end of the Igh-.gamma. gene complex, which in the absence of T cells have a low probability of being switched to, are the most influenced by T cell help.