T CELL REGULATION OF THE Ig CLASS SWITCH

Signals from thymus-processed T cells are important in determining the quantities of various immunoglobul in (Ig) classes of ant ibody (Ab) 1 synthesized in response to antigen (1-6). We have recently reported that T cells can preferentially enhance the production of certain IgG isotypes, namely IgG2a, in the B cell response to the type 2 T-independent (TI-2) antigen, 2 trinitrophenyl (TNP)-Ficoll (7). Thymus-processed T cells were not manda to ry for IgG synthesis in the response to TNP-Ficoll , since a thymic nude mice could mount IgG an t i -TNP responses to this antigen, including a weak IgGza response. Interestingly, the relative amount of Ab in each of the several IgG classes produced by nude mice to TNP-Ficoll was found to correlate with the 5' to 3' gene order for the various IgG heavy chain constant region genes (9, 10), i.e., IgG3 > IgG1 > IgG2b > IgG2~. This suggested that the relative proximity of a given IgG heavy chain (Igh-y) gene to the switch sites located 5' to the Igh-~ gene (11, 12) may influence the frequency of specific isotype switching events that take place within a TNP-Ficoll-responsive B cell clone. The relative effectiveness o f T cells at enhancing Ab secretion within each of the IgG classes appeared to correlate inversely with the relative amount o f Ab produced in the absence o f T cells, i.e., help for IgG2~ synthesis > help for IgG2b synthesis > help for IgG1 synthesis. One possible explanation for these results is that T cells provide additional signals to TNP-Ficoll-responsive B cells to enhance switching events within the expanding B cell clones. Thus, isotype-switching events that occur with low frequency in the absence of T cells, e.g., the switch to IgG2a, may be the most affected by ancillary T