Autoreactive isotype-specific T cells determine B cell frequency

Suppressive activities involving T-B and T-T cell interactions are important to maintain immune system homeostasis. Negative control of IgG2a(b+) B cells by anti-IgG2a(b) T cells derived from Igha mice has been well documented. Nevertheless the real contribution of anti-IgG2a(b) T cells, endogenously matured in Igh(b) mice, in controlling IgG2a(b+) B cell function has never been investigated. We previously generated anti-IgG2a(b) TCR-transgenic mice and showed that transgenic T cells were not deleted in the thymus and that they were responsible for a complete and chronic IgG2a(b) suppression. Here we show that T cells expressing high density of anti-IgG2a(b) TCR were positively selected in the thymus with a higher efficiency in animals expressing IgG2ab, reached peripheral lymphoid organs and negatively controlled IgG2a(b) serum levels. Moreover, anti-IgG2a(b) T cells transgenic for the single TCR beta chain, thus undergoing normal alpha rearrangements and normal processes of selection, also reached the periphery and suppressed IgG2a(b). Interestingly, concentration of IgG2a(b) in serum inversely correlated with the peripheral frequency of Ig-specific T cells. Finally, T cells able to suppress IgG2a(b) were obtained from Ighb non-transgenic mice, indicating that anti-gamma 2a(b) T cells are naturally present in the periphery of Ighb animals. We propose that IgG2a(b)-specific T cells contribute to determine IgG2a(b) serum levels in Ighb mice.