B LYMPHOCYTE ACTIVATION

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The immediate goals are to delineate the mechanisms by which functionally important molecules such as Lyb2, Ia and BSF-1 receptors participate in B lymphocyte activation. Long term goals are to devise ways to regulate B cell function in hyper- and hypo-immune states as well as to define the biochemical basis of B cell growth and differentiation using the approaches of biochemistry, cellular immunology and molecular biology. The long term objectives of this research are to understand the underlying basis for the immune abnormalities associated with age. Initially, the focus of the research will be the functional role of two B cell surface molecules Lyb2 and Ia. Strategies will be developed to clone the gene for Lyb2 antigen. The concept that a unique B cell subset is involved in antibody responses to polysaccharide antigens will be evaluated. The possibility that B cell subsets may differ in the growth or maturation factor receptors they express will be studied by preparing monoclonal antibodies to such B cell surface molecules. Biochemical and phenotypic abnormalities in B cells from aged mice will be studied. The repertoire differences in B cells from young and aged mice will be determined by quantitating the expression of the murine heavy chain variable region gene families by nucleic acid hybridization techniques. These studies should enable us to better understand B cell growth and differentiation and to develop better strategies for immunomodulation.