Possible interactions between the Fc epsilon receptor and a novel mast cell function-associated antigen.
We have recently described a monoclonal antibody, mAb G63, which identifies a novel membrane component of mast cells. This antigen is a glycoprotein with an apparent molecular mass of 28-40 kd, and is present on the surface of rat mucosal and serosal mast cells. Its density on cells of the mucosal mast cell line RBL-2H3 is 1 - 2 x 10(4) copies per cell. Crosslinking of this membrane protein by the intact mAb G63 results in a pronounced inhibition of the Fc epsilon RI-mediated secretion of RBL-2H3 cells. Here we show that crosslinking this novel membrane component inhibits biochemical processes initiated by Fc epsilon RI aggregation, such as the hydrolysis of phosphatidylinositides, the influx of Ca2+ ions, and the synthesis and release of de novo formed inflammatory mediators. Furthermore, by fluorescence microscopy, we show that crosslinking of Fc epsilon RI-IgE complexes by multivalent antigen results in redistribution of the membrane component recognized by G63, leading to its co-localization with the aggregated Fc epsilon RI. This localization is inhibited by NaN3, but not by colchicine or cytochalasin D. Fc epsilon RI crosslinking also promotes internalization of this novel membrane component. Taken together these data suggest that the mast cell membrane component recognized by mAb G63 is involved in the Fc epsilon RI-mediated stimulation of these cells, and thus can be considered a mast cell function-associated antigen (MAFA).
Ortega
E
E
Department of Chemical Immunology, Weizmann Institute of Science, Rehovot, Israel.
Schneider
H
H
Pecht
I
I
D000818:Animals; D000911:Antibodies, Monoclonal; D000944:Antigens, Differentiation, B-Lymphocyte / Q000378:metabolism*; D000954:Antigens, Surface / Q000378:metabolism*; D003432:Cross-Linking Reagents; D005455:Fluorescent Antibody Technique; D007073:Immunoglobulin E / Q000378:metabolism*; D008407:Mast Cells / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000276:immunology / Q000378:metabolism*; D011961:Receptors, Fc / Q000378:metabolism*; D017455:Receptors, IgE
D000911:Antibodies, Monoclonal; D000944:Antigens, Differentiation, B-Lymphocyte; D000954:Antigens, Surface; D003432:Cross-Linking Reagents; D008562:Membrane Glycoproteins; D011961:Receptors, Fc; D017455:Receptors, IgE; D007073:Immunoglobulin E