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Immunity. 2008 Oct 17;29(4):615-27. doi: 10.1016/j.immuni.2008.07.016. Epub 2008 Oct 2.

Fas receptor expression in germinal-center B cells is essential for T and B lymphocyte homeostasis.

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Campbell Family Institute for Cancer Research, Ontario Cancer Institute, University Health Network, Toronto, Ontario, Canada.


Fas is highly expressed in activated and germinal center (GC) B cells but can potentially be inactivated by misguided somatic hypermutation. We employed conditional Fas-deficient mice to investigate the physiological functions of Fas in various B cell subsets. B cell-specific Fas-deficient mice developed fatal lymphoproliferation due to activation of B cells and T cells. Ablation of Fas specifically in GC B cells reproduced the phenotype, indicating that the lymphoproliferation initiates in the GC environment. B cell-specific Fas-deficient mice also showed an accumulation of IgG1(+) memory B cells expressing high amounts of CD80 and the expansion of CD28-expressing CD4(+) Th cells. Blocking T cell-B cell interaction and GC formation completely prevented the fatal lymphoproliferation. Thus, Fas-mediated selection of GC B cells and the resulting memory B cell compartment is essential for maintaining the homeostasis of both T and B lymphocytes.

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