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 Th1 lymphocytes, while inducing the selective expansion of antigen-specific Th2 cells. Several parameters of tolerance induction were analyzed in this work, in order to establish whether B cell tolerance and Th1 unresponsiveness were functionally related in this in vivo model. By varying the antigen form and site of injection, we demonstrate in this work that Th1 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 while displaying a defective Th1 response. In fact, these animals developed a strong Th2 response in vivo, demonstrating that selective expansion of antigen-specific Th2 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 Th2-type helper cells in vivo irrespectively of the B cell tolerance status.