The Journal of Experimental Medicine
Avanti Polar Lipids
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Journal of Experimental Medicine, Vol 184, 1639-1649, Copyright © 1996 by Rockefeller University Press

ARTICLES

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

MS Chappel, MR Hough, A Mittel, F Takei, R Kay and RK Humphries
Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver.

The murine heat-stable antigen (HSA) is a glycosyl-phosphatidylinositol- linked cell surface protein which has been implicated in cellular adhesion processes, the co-stimulation of CD4+ T cells, and B cell memory. We have recently demonstrated a significant reduction in pro-B and pre-B lymphocytes in transgenic mice that overexpress HSA. We now report that cross-linking HSA with the M1/69 monoclonal antibody induces the apoptosis of cultured B cell precursors in a stomal cell and cytokine-independent manner and that sensitivity to HSA-mediated cell death 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 together, these data implicate HSA as a potent negative regulator of B cell development and activation.
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