NCI PHYSICIAN-INVESTIGATOR DEVELOPMENT AWARD PROGRAM

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The overall aim of this project is the functional characterization of cell surface antigens expressed on activated but not resting human B lymphocytes. These antigens are excellent candidates for cell surface structures which control B cell activation, proliferation, and differentiation. This proposal will involve a detailed analysis of B cell activation antigens with specific attention to: 1) the stimuli which induce their expression, 2) their relationship to other B cell antigens expressed on both resting and activated B cells, 3) their relationship to growth and differentiation factors which are involved in the proliferation of B cells and stimulation of immunoglobulin secretion, and 4) the expression of these antigens on neoplastic B cells, and their possible role in neoplastic B cell proliferation. To accomplish this, monoclonal antibodies to previously known and new B cell activation antigens will be developed, and extensively characterized. The expression of these antigens will be related to the stages of B cell activation/proliferation and differentiation, and more importantly an attempt will be made to define the functional importance of these antigens. Finally, the expression of B cell activation antigens will be examined on B cell leukemias and lymphomas. This will be done in order to determine whether there is a correlation between antigen expression on neoplastic B cells and both the ability to respond to physiologic triggers of activation/proliferation in vitro as well as the clinical presentation and course of disease.