J. Exp. Med.
© The Rockefeller University Press
0022-1007/97/10/1307/08 $2.00
Volume 186, Number 8, October 20, 1997 1307-1314

Negative Regulation of FcRI-mediated Degranulation by CD81

By Tony J. Fleming, Emmanuel Donnadieu, Chang Ho Song, Francois Van Laethem, Stephen J. Galli, and Jean-Pierre Kinet

From the Departments of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215

Signaling through the high affinity receptor for immunoglobulin E (FcRI) results in the coordinate activation of tyrosine kinases before calcium mobilization. Receptors capable of interfering with the signaling of antigen receptors, such as FcRI, recruit tyrosine and inositol phosphatases that results in diminished calcium mobilization. Here, we show that antibodies recognizing CD81 inhibit FcRI-mediated mast cell degranulation but, surprisingly, without affecting aggregation-dependent tyrosine phosphorylation, calcium mobilization, or leukotriene synthesis. Furthermore, CD81 antibodies also inhibit mast cell degranulation in vivo as measured by reduced passive cutaneous anaphylaxis responses. These results reveal an unsuspected calcium-independent pathway of antigen receptor regulation, which is accessible to engagement by membrane proteins and on which novel therapeutic approaches to allergic diseases could be based.

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