PMID: 9186658Apr 5, 1997Paper

Unique site of autoantibody production in Fas-deficient mice

Annals of the New York Academy of Sciences
B A JacobsonA Marshak-Rothstein

Abstract

The inability of B and T lymphocytes from mice expressing the lpr mutation to express functional Fas on their cell surface leads to an immunoregulatory defect associated with excessive autoantibody production. Nevertheless, T-dependent antibody response to foreign antigens in these mice appears relatively normal. To better understand exactly how Fas/FasL interactions control autoantibody production, studies were undertaken to determine (1) what kind(s) of B cells are sensitive to Fas-mediated apoptosis and (2) where the autoantibody-producing cells in lpr mice are located. We found that B cells activated by CD40L are extremely sensitive as targets in assays of Th1 CMC. However, B cells that receive a complete signal through their sIgM antigen receptor acquire a FasL-resistant phenotype. In situ analysis of splenic sections from lpr mice demonstrated that autoantibody-producing cells were uniquely localized to the T cell-rich inner PALS. A similar distribution pattern of IgG AFC was found in mice with chronic GVH disease. These data are consistent with the premise that the inner PALS, and not the germinal center, is the major site of FasL regulation of B cell activity and that, as a result of genetic or inducible loss of sensiti...Continue Reading

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Citations

Dec 22, 1999·Oncogene·M Barkett, T D Gilmore
Apr 9, 2002·The Journal of Immunology : Official Journal of the American Association of Immunologists·Debora R SekiguchiRobert A Eisenberg
Aug 24, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·Robert A BarringtonMichael C Carroll

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