Immunoglobulins of the IgA class are important in the specific immune defense of mucosal surfaces and perhaps in the regulation of secretory immunity. However, the mechanicsms involved in these activities are still incompletely understood. The recent demonstration that lymphocytes and effector cells populations display receptors for the Fc portion of IgA (RFc), suggests that these receptors may mediate interactions between IgA and/or IgA-antigen complexes and the effector or regulatory cell expressing RFc. The present proposal is directed toward an evaluation of the function of RFc and RFc - bearing human leukocyte subpopulations. We would first quantitate the expression of this receptor on various lymphocyte subpopulations and on leukocytes from peripheral blood and mucosal surfaces. Since the quantity of RFc per cell may be related to its functional activity, we would examine the ability of various mediators of immune function including supernatants from stimulated lymphocytes, immunoglobulins and immunoglobulin-antigen complexes to modulate expression of RFc on these cells. RFc would be isolated and partially characterized. Monoclonal antibodies to RFc would be prepared and used for further characterization of these receptors, and in studies of their function. The regulatory and effector properties of cells bearing RFc would be examined and the role of RFc in these functions would be determined. These studies would be performed on cells from peripheral and mucosal lymphoid tissues before and after modulation of RFc expression. In addition, myeloid cell-specific monoclonal antibodies would be used to isolate subpopulations of monocytes and PMNs for the subsequent analysis of the ability of these groups of cells to manifest RFc -dependent effector functions. The data obtained in these studies on RFc and RFc -bearing leukocyte subpopulations should enhance our understanding of the regulation and expression of secretory immunity.
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