B cell-deprived mice lack functional expression of certain T suppressor cell subsets

The generation of functionally active immunoregulatory T lymphocytes has been shown to depend upon the interaction of a number of different immune cell types during development. In order to understand and perhaps manipulate immunoregulatory T cell interactions, it is important to identify the nature and role of these cell types in the immunoregulatory T cell pathway. We have investigated the role of Ig+ B cells in the generation of suppressor T lymphocytes in the immune response to SRBC. Our approach was to suppress the expression of Ig+ B cells in experimental mice by continuously treating these animals with a rabbit anti-mu-chain antiserum. These animals were simultaneously tested for their ability to make suppressor T cell responses as measured by the ability to produce or accept SRBC-specific suppressor T cell factors. This particular approach, neonatal suppression with anti-mu-chain antibody, has been previously shown to be an effective means of depleting animals of Ig+ cells, while having little or no effect on a number of different T cell-mediated responses, including T cell mediated allograft rejection and delayed-type hypersensitivity responses in vivo as well as the generation of MLR and CTL responses to alloantigens and conventional I-A recognizing T helper cell responses in vitro. Our results indicate that anti-mu-treated mice lack the ability to produce both Ly1 and Ly2 cell-derived suppressor factors when immunized with the relevant antigen SRBC. Further, while the T cells from anti-mu-treated mice were capable of generating a T helper cell response to SRBC in vitro, these T cells no longer responded to suppressor cell signals from either the Ly1 or Ly2 T cell-derived suppressor factors. The ability to produce or accept suppressor cell signals was traced to the lack of an I-J+ Ly1 T cell absent in anti-mu-treated mice. This cell produces an I-J+ antigen nonspecific molecule which imparts Igh-V linked genetic restrictions to both the Ly1 and Ly2 T cell derived suppressor factors. The results alter our view on immune regulation by suggesting that both the induction and effector phase of suppressor T cell activity to SRBC is dependent upon an antigen nonspecific Ly1 I-J+ T cell which is distinct from the antigen recognizing I-J- T cells required for antigen-specific suppression. This I-J+ T cell, which imparts an Igh-linked restriction to the suppressor factors, is critically dependent on Ig+ B cells to reach a functionally active state.(ABSTRACT TRUNCATED AT 400 WORDS)