Following stimulation with antigen or polyclonal mitogen, resting human B lymphocytes become activated, proliferate, and subsequently differentiate into antibody secreting cells. This sequence can be delineated by a series of morphologic, metabolic, molecular, and cell surface antigenic events. The focus of this proposal is to study the function of those cell surface structures which are not expressed on resting B cell but appear with activation. These activation antigen (ActAgs) are excellent candidates for those structures which may have a regulatory role in the control of B cell proliferation and differentiation or are involved in cell-cell interactions, in localization, or in adhesion of activated B cells within a microenvironment.
The aims of the present project are to examine the function of selected B cell activation antigens by: 1) examining the response of activated B cell populations to growth and differentiation factors; 2) developing monoclonal antibodies (MAbs) directed against previously described ActAgs in an attempt to identify functionally important epitopes; 3) using MAbs directed against ActAgs to induce or inhibit proliferation and/or differentiation in vitro; and 4) using MAbs directed against ActAgs to determine whether the molecule is involved in cell-cell interactions. To achieve the first aim, I will identify and isolate populations of B cells which express an ActAg and examine their responses in B cell functional assays. For the second aim, I will utilize novel immunization techniques employing B cell ActAg cDNA transfected into cos cells. In the third and fourth specific aims, I will attempt to examine the function of the Ag using MAbs to mimic natural ligands or inhibit cell-cell interactions. These studies should provide a biologic basis with which to eventually examine human B cell malignancies as subpopulations of activated B cells and to attempt to correlate their clinical presentation and disease course with the subpopulation of B cells from which they are derived.
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