Biomedical Frontiers: Winter 1994, Vol.1, No.2
Deciphering T and B Cell Discourse

T and B cells give new meaning to cellular communication. B cells make antibodies because T cells secrete cytokine messages to them. Direct contact between B and T cells is also critical in antibody expression. While cytokines have received a lot of attention as therapeutics for immune disorders, contact between T and B cells is also a target for intervention in diseases with excessive or deficient antibody production.

To that end, Dr. Leonard Chess, professor of medicine, and Dr. Seth Lederman, assistant professor of medicine, have been studying a T cell surface protein (T-BAM or T cell-B cell activating molecule) they identified in 1992 that acts by direct cellular contact with B cells so they make appropriate immunoglobulin molecules. They also isolated a monoclonal antibody (MAb) against T-BAM which inhibits the direct cellular action of T cells on B cells.

In a recent trial--funded by a Columbia-Presbyterian Medical Center clinical trials grant--Dr. Lederman found T-BAM is expressed only in T cells in lymph nodes and at inflammation sites. One implication of this finding is that a MAb to T-BAM could treat autoimmune disease where autoantibodies play an important role in pathogenesis. Since the T-BAM-MAb will act on T cells in their transient process of assisting B cells, the MAb could inhibit autoantibody response without hurting other non-T-BAM expressing T cells.

Other studies (International Immunology, Vol. 5, No. 7, July 1993, p. 769) also show T-BAM's importance in vivo. In this report, patients with an X-linked deletion for the T-BAM (also known as CD40 ligand, CD40 being the receptor on B cells for CD40) could not switch from an IgM/IgD immunoglobulin type to IgG, IgA, and IgE. Future experiments will see if giving the T-BAM gene to the T cells of these patients can induce immunoglobulin switching in their B cells.

A patent is pending on the diagnostic and therapeutic implications of the findings of Drs. Chess and Lederman.