Visualization of Direct T-B Cell Interaction

Abstract

The concept that an antigen-specific helper T cell directly binds to a B cell stimulated by the same antigen and that this direct interaction is essential for B cell antibody production is well accepted. The most convincing evidence until recently that such cell-cell contact was necessary came from studies of Mitchison (1971) and his colleagues, subsequently repeated in numerous permutations, which showed that the epitopes recognized by both the T cell and B cell must be present on the same molecule. The current picture we have of the events in this interaction is that the specific immunoglobulin on the B cell binds determinants on the antigen, that the antigen is internalized and processed into fragments, and that these fragments are somehow presented on the B cell surface in association with class II. A helper T cell then recognizes the antigen fragment-class II complex by virtue of its specific receptor and thus a direct interaction of the two cells occurs. The recognition of antigen/class II activates the T cells and stimulates the T cell to synthesize and secrete lymphokines. Both the direct interaction of the T cell with the B cell and the soluble lymphokines secreted by the helper T cell are considered essential for B cell activation and subsequent proliferation and differentiation to antibody secretion. Despite the wide acceptance of this scenario actual T-B cell interactions have not been directly visualized until recently, and the details of the interaction and its consequences are largely unknown. In this report, I will review several recent studies we have done in collaboration with our colleagues, Dr. Abraham Kupfer, Dr. Charles Janeway and Dr. Jonanthan Singer. These studies reveal several striking events which occur during specific T cell-B cell interaction.