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

In the absence of T cells, B cells were found to respond to the type 2 T-independent (TI-2) antigen, trinitrophenyl (TNP)-Ficoll, with a characteristic hierarchy of IgM and IgG subclass Ab production which directly correlated with 5' to 3' Igh-C gene order, i.e., IgM greater tha IgG3 greater than IgG1 greater than IgG2b greater than IgG2a. This was evident when immune serum Ab titers were analyzed, when in vitro secretion of antibody from immune cells was measured and when TNP- Ficoll-stimulated clones in a splenic focus assay were analyzed for isotype production. T cells were found to cause a preferential relative increase in the amount of IgG2a antibody 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 were found to increase 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 whose genes are encoded 5' to the Igh-gamma 2a gene. The data are discussed in terms to T cell enhancement of IgG2a Ab synthesis being 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.