REGULATORY MECHANISMS IN THE IMMUNE RESPONSE

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The aims of this proposal are to understand in detail the means whereby T cells help B cells respond to antigen. We are particularly interested in two processes which occur; first, the events which initiate B cell response and secondly, the effects on B cells of the lymphokine B cell stimulating factor-1 (BSF1). Although lymphokines alone can drive the responses of B cells to some antigens responses of B cells to many antigens, particularly those born on proteins, require the presence of carrier-specific T cells as well as lymphokines. These T cells appear to be involved chiefly at the beginning of the B cell response. they may be acting by secreting some hitherto undiscovered lymphokine or by direct contact of their own membrane proteins with ligands on T or B cells and/or isolated membrane proteins, we plan to investigate which of these possibilities is correct. Membrane components to be studied will include the T cell receptor, L3T4, LFA-1 and Class II molecules. For example, we will isolate receptors from a particular helper T cell hybridoma and test by various strategies whether these receptors bind antigen plus MHC. These receptors will be used in liposomes or after transfer to another T cell hybridoma to test for antigen-specific helper activity. BSF1 has a number of effects on B cells. It induces Ia synthesis in resting cells, and stimulates proliferation of sub-maximally activated B cells. We plan to isolate the receptor for BSF1 on B cells, and study in detail the inductive effects of this lymphokine no resting cells.