The overall aim of the project is the characterization of functionally important cell surface antigens (Ags) expressed on activated human B lymphocytes. The research project's interest in these molecules is based on the notion that these Ags are prime candidates for those cell surface structures which control B-cell activation, proliferation, and differentiation. In the proposal, it is planned to undertake a detailed analysis of B-cell activation Ags with specific attention to: (1) the stimuli that induce their expresssion; (2) their relationship to other B-cell Ags expressed on both resting and activated B cells; (3) their relationship to growth factor and/or accessory cells that are involved with activation, proliferation, and differentiation of B cells; and (4) the expression of the Ags on neoplastic B cells and their possible role in the induction and control of B-cell neoplasia. To accomplish this, research is planned to develop methods to isolate and activate human B cells in vitro and develop culture systems which will allow delineation of the cell surface antigenic changes which accompany activation, proliferation, and differentiation. Using the expression of these cell surface Ags to identify the stages of B-cell activation, the attempt will be made to isolate unique populations of activated B cells and study their response to inducers of activation and differentiation. The goals are to: (1) identify and characterize those cell surface molecules which are important in the induction of these processes; (2) study previously known B-cell activation Ags; (3) develop monoclonal antibodies to new activation Ags with the intention of relating these structures to the stages of B-cell activation and differentiation as well as defining the functional importance of each of these molecules; (4) examine the expression of B-cell activation Ags on B-cell leukemias and lymphomas; and (5) attempt to determine whether there is a correlation between antigen expression on neoplastic B cells and whether they have both the ability to respond to physiologic triggers of activation in vitro as well as the clinical course of the disease. (AG)
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