Cooperative interaction of B lymphocytes with antigen-specific helper T lymphocytes is MHC restricted

Abstract

To produce antibody, bone-marrow-derived (B) lymphocytes generally require the synergistic action of a thymus-derived (T) lymphocyte, termed a helper T cell (Th)¹. The interaction of Th with B cells is antigen specific and requires that both the T and the B cell be specific for physically linked antigenic determinants². More recently it has been demonstrated in numerous systems that the interaction of Th and B cells is governed by antigens encoded within the major histocompatibility complex (MHC), such that Th and B cells must be identical in the I region of the MHC in order to cooperate efficiently^3–5. This finding has been termed MHC restriction. However, studies using populations of T cells as a source of Th could be influenced by the presence of alloreactive T cells, suppressor T cells and other T-cells subsets, thus making interpretation difficult. Moreover, it has been proposed⁶ that MHC restriction governs not the interaction of Th with B cells, but rather the interaction of Th cells with antigen-presenting cells (APCs), whereafter the interaction of Th with B cells is said to be unrestricted. We have now attempted to clarify this situation by examining the interaction of soft agar colonies and clones of antigen-specific, MHC-restricted proliferating T cells^7,8 with purified B cells using several different assays. We conclude that the antigen-specific cooperative interactions between Th and B cells are themselves MHC restricted, and that B cells bearing the wrong MHC-encoded antigens cannot be activated by addition of APCs matched to the Th cell but differing from the B cell at MHC.