CROSS-LINKING THE MURINE HEAT-STABLE ANTIGEN INDUCES APOPTOSIS IN B-CELL PRECURSORS AND SUPPRESSES THE ANTI-CD40-INDUCED PROLIFERATION OF MATURE RESTING B-LYMPHOCYTES

The murine heat-stable antigen (HSA) is a glycosyl-phosphatidylinosito l-linked cell surface protein which has been implicated in cellular ad hesion processes, the co-stimulation of CD4(+) T cells, and B cell mem ory. We have recently demonstrated a significant reduction in pro-B an d pre-B lymphocytes in transgenic mice that overexpress HSA. We now re port that cross-linking HSA with the M1/69 monoclonal antibody induces the apoptosis of cultured B cell precursors in a stomal cell and cyto kine-independent manner and that sensitivity to HSA-mediated cell deat h increases with developmental maturity. The cross-linking of HSA does not induce apoptosis in mature splenic B cells, but instead inhibits their ability to proliferate in response to anti-CD40 + IL-4. Taken to gether, these data implicate HSA as a potent negative regulator of B c ell development and activation.