Douglas FearonWellcome Trust Immunology Unit, University of Cambridge School of Clinical Medicine, Cambridge, UK F1000 Head of Faculty (since 01 November 2001)
BIOGRAPHYWe wish to understand how the germinal centre reaction of B lymphocytes occurs. In this response to T-dependent antigens, there is marked clonal expansion of antigen-specific B lymphocytes, hypermutation of the immunoglobulin genes with selection for high affinity mutants, the generation of memory B lymphocytes, and the maturation of B lymphocytes into long-lived plasma cells that migrate to the bone marrow. We are examining the roles of certain genes that are differentially expressed in the germinal center B cell by in vitro techniques using retroviral transduction of primary and transformed lymphocytes, and in vivo using inducible, transgenic systems.
A second area of research is the role that innate immunity plays in the selection of antigens for adaptive immune responses. We have found that the innate immune system of complement can increase by approximately 1000-fold the immunogenicity of a model antigen, and we have recently found evidence suggesting that neutrophils can alter antigens to increase its capacity to elicit an adaptive immune response. We hope that this work will lead to the development of more potent vaccines, and perhaps an understanding of how infections induce autoimmunity.
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