Fas Receptor Expression in Germinal-Center B Cells Is Essential for T and B Lymphocyte Homeostasis

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 deve...

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Bibliographic Details
Published in:Immunity (Cambridge, Mass.) Mass.), 2008-10, Vol.29 (4), p.615-627
Main Authors: Hao, Zhenyue, Duncan, Gordon S, Seagal, Jane, Su, Yu-Wen, Hong, Claire, Haight, Jillian, Chen, Nien-Jung, Elia, Andrew, Wakeham, Andrew, Li, Wanda Y, Liepa, Jennifer, Wood, Geoffrey A, Casola, Stefano, Rajewsky, Klaus, Mak, Tak W
Format: Article
Language:English
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Summary: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 super(+) memory B cells expressing high amounts of CD80 and the expansion of CD28- expressing CD4 super(+) 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.
ISSN:1074-7613
DOI:10.1016/j.immuni.2008.07.016Article</h4>