INDUCTION OF T(H)2 RESPONSES TO SOLUBLE-PROTEINS IS INDEPENDENT OF B-CELL TOLERANCE STATUS

Injection of high doses of monomeric human gamma globulins (dHGG) in n aive, adult mice causes antigen-specific tolerance of B cell and T(h)1 lymphocytes, while inducing the selective expansion of antigen-specif ic T(h)2 cells. Several parameters of tolerance induction were analyze d in this work, in order to establish whether B cell tolerance and T(h )1 unresponsiveness were functionally related in this in vivo model. B y varying the antigen form and site of injection, we demonstrate in th is work that T(h)1 unresponsiveness to HGG is not a consequence of per ipheral B cell tolerance. In particular, mice pretreated with heat-agg regated antigen (HAHGG) or F(ab')(2) HGG were found to develop a stron g humoral response white displaying a defective T(h)1 response. In fac t, these animals developed a strong T(h)2 response in vivo, demonstrat ing that selective expansion of antigen-specific T(h)2 cells in this m odel is not a consequence of B cell tolerance or antigen capture by Fc receptor-expressing cells. We conclude that while B cell tolerance in this model is only observed in response to deaggregated antigen, inje ction of all forms of adjuvant-free, protein antigens induces T helper precursor cells to differentiate into T(h)2-type helper cells in vivo irrespectively of the B cell tolerance status.