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

Zhenyue Hao*, Gordon S. Duncan, Jane Seagal, Yu Wen Su, Claire Hong, Jillian Haight, Nien Jung Chen, Andrew Elia, Andrew Wakeham, Wanda Y. Li, Jennifer Liepa, Geoffrey A. Wood, Stefano Casola, Klaus Rajewsky, Tak W. Mak

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

180 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)615-627
Number of pages13
JournalImmunity
Volume29
Issue number4
DOIs
StatePublished - 17 Oct 2008

Keywords

  • CELLIMMUNO

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