In both man and mouse it has been shown that the early repertoire of T and B cells differs considerably from that of the adult with respect to V gene family expression, the specificity of receptors and the functions and phenotypes of both lineages. In this proposal we will continue to analyze the developmental regulation of the B cell repertoire in mice. We propose that the Ly1+ B cell subset is a separate lineage of beta cells derived from the omentum and that these cells are primarily responsible for the establishment of the early beta cell repertoire. We will also determine whether the omentum is involved in the extrathymic generation of subsets of T cells. We will investigate at a molecular and cellular level the specificities and lymphocyte activating properties of antibodies produced by these cells as well as their potential to synthesize interleukins which may be involved in the regulation of growth and differentiation of other lymphoid cells. These studies will focus on the origin of these subpopulations of lymphocytes, their role in the ontogeny of the immune response and maintenance of the Beta and T cell repertoires. These experiments may reveal in the long-term why deregulation of Lyl and CD5+ B cells are involved in certain autoimmune and Beta cell neoplastic diseases in mouse and similar diseases in man.
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