Faculty Lecture Series

When	Wednesday, February 10, 2010 5 PM - 6 PM
Where	Valerie Timken Amphitheater Green Hospital
Who		Ann Feeney, Ph.D. Professor, Department of Immunology and Microbial Science
Topic	"Genetic and Epigenetic Regulation of Antigen Receptor Gene Rearrangement"
	In order to protect us against a wide variety of pathogens, the immune system has evolved the ingenious process of V(D)J recombination to encode millions of different antigen receptors from a minimum amount of our genome. The antigen receptors are encoded by gene segments, called V, D and J genes, and in each precursor lymphocyte, a different set of V, D, and J genes recombine at the level of genomic DNA to form exons encoding the heterodimeric antigen receptor. I will describe our studies elucidating the many levels of regulation of this process, both genetic and epigenetic. The accessibility of individual genes, and of parts of each receptor locus, are under tight control so that only certain groups of genes are available to rearrange at any given time. Finally, in addition to these genetic and epigenetic levels of regulation, there is emerging evidence that the 3-dimensional structure of the antigen receptor loci changes transiently during the process of V(D)J recombination by contracting to bring the hundreds of V genes spread over the 2-3 megabase loci into close proximity to the DJ genes to which they need to recombine. Together, these genetic and epigenetic factors result in the finely orchestrated process of V(D)J rearrangement which creates a diverse antibody and T cell receptor repertoire.
Selected Publications
	Feeney, A.J. Genetic and epigenetic control of V gene rearrangement frequency. Adv. Exp. Med. Biol. 650:73-81, 2009.
	Degner, S.C., Wong, T.P., Jankevicius, G., and Feeney, A.J. Cutting Edge: Developmental stage-specific recruitment of cohesin to CTCF sites throughout immunoglobulin loci during B lymphocyte development. J. Immunol. 182:44-48, 2009.
	Xu, C.-R. and Feeney, A.J. The epigenetic profile of immunoglobulin genes is dynamically regulated during B cell differentiation and is modulated by pre-BCR signaling. J. Immunol. 182:1362-1378, 2009.
	Xu, C.-R., Schaffer. L., Head, S.R. and Feeney, A.J. Reciprocal patterns of methylation of H3K36 and H3K27 on proximal vs. distal IgV_H genes are modulated by IL7 and Pax5. Proc Natl Acad Sci USA 105:8685-8690, 2008
	Espinoza, C.R. and Feeney, A.J. Chromatin accessibility and epigenetic modifications differ between frequently and infrequently rearranging V_H genes. Mol. Immunol. 44: 2675-2685, 2007.