My laboratory studies two aspects of lymphocyte development and diversification. The production of a diverse repertoire of immunoglobulin molecules is of paramount importance to the maintenance of a functional immune system. One project in my laboratory focuses on B cell development and mechanisms of generation of immunoglobulin diversity in cattle. Unlike mouse and human, species that generate diversity by the rearrangement of numerous gene segments, cattle appear to use a recombinational mechanism known as gene conversion to generate a diverse repertoire of immunoglobulin molecules. In addition to this novel mechanism of generating diversity, B cell development in cattle appears to differ from that observed in mouse and human; B cell development occurs in the ileal Payer’s patch, a specialized lymphoid organ, rather than in the bone marrow. Experiments designed to elucidate the exact mechanisms of diversification and processes that regulate B cell development are ongoing. Another area of active investigation in my laboratory is elucidation of the molecular events required for the induction of apoptosis in the mouse thymus. Negative selection (the removal of autoreactive T cells) occurs by an active cell death process known as apoptosis. To isolate genes that are required for this process, we constructed a cDNA library from dying thymocytes and isolated several genes that are induced or repressed during apoptosis. We have shown that several of these genes, such as p53 and nur77, are required for cell death. Using techniques such as yeast two-hybrid analysis, we are now asking how these genes mediate cell death in T cells. Our current focus is a broader understanding of the roles played by these critical genes during apoptosis.