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    The gut environment obviates obligatory signals for germinal center formation and somatic hypermutation in the Peyer's patches

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    Author
    Basu, Subhendu
    Advisor
    Cerny, Jan, 1939-
    Date
    2003
    Type
    dissertation
    
    Metadata
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    Abstract
    Germinal center (GC) reaction and somatic mutation in the spleen in response to protein antigens is absolutely dependent on help from antigen-specific CD4+ T lymphocytes and stimulation of B cells via the CD19 co-receptor. However, the absence of CD4 T cell help apparently does not abrogate the GC formation in the Peyer's patch. The present study makes use of normal, CD4-null and CD 19-null mice to test the hypothesis that activation of somatic mutation in P. patch is independent of conventional co-stimulation. Splenic GC were induced by immunization with the hapten, nitrophenyl coupled to a protein carrier. The GC B cells were micro-dissected from tissue sections and the rearranged Vlambda1Jlambda1 genes were amplified and sequenced. The CD4-null and CD19-null mice failed to form GC in the spleen but the GC in the P. patches of these mice were comparable in number and average mutation frequency to antigen-driven splenic GC in the normal mice. It was determined that the GC formation in the P. patches was dependent on help from alphabeta T cells and that gammadelta T cells were not involved in providing this help. Adoptive transfer of the splenic T cells from CD4-null mice into T deficient mice resulted in GC formation in the P. patch but not in the spleen. Therefore, the presence of GC in the P. patch of CD4-null mice was not due to a special T cell population but a function of the unique gut environment since the splenic T cells can provide the requisite help for GC formation when present in the P. patch. It is apparent that obligatory stimuli for splenic GC formation and somatic mutation are dispensable in P. patches.
    Description
    University of Maryland, Baltimore. Microbiology and Immunology. Ph.D. 2003
    Keyword
    Health Sciences, Immunology
    Germinal Center--physiology
    Mutation
    Peyer's Patch--immunology
    Identifier to cite or link to this item
    http://hdl.handle.net/10713/1130
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    Theses and Dissertations All Schools
    Theses and Dissertations School of Medicine

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