Induction of Th2 responses to soluble proteins is independent of B cell tolerance status

Injection of high doses of monomeric human gamma globulins (dHGG) in naive, adult mice causes antigen-specific tolerance of B cell and T(h)1 lymphocytes, while inducing the selective expansion of antigen-specific T(h)2 cells. Several parameters of tolerance induction were analyzed in this work, in order to establish whether B cell tolerance and T(h)1 unresponsiveness were functionally related in this in vivo model. By varying the antigen form and site of injection, we demonstrate in this work that T(h)1 unresponsiveness to HGG is not a consequence of peripheral B cell tolerance. In particular, mice pretreated with heat-aggregated antigen (HAHGG) or F(ab')(2) HGG were found to develop a strong humoral response white displaying a defective T(h)1 response. In fact, these animals developed a strong T(h)2 response in vivo, demonstrating that selective expansion of antigen-specific T(h)2 cells in this model 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, injection 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