B cells drive lymphocyte activation and expansion in mice with the CD45 wedge mutation and Fas deficiency

Vikas A. Gupta, Michelle L. Hermiston, Gail Cassafer, David I. Daikh, Arthur Weiss

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

CD45 and Fas regulate tyrosine phosphorylation and apoptotic signaling pathways, respectively. Mutation of an inhibitory wedge motif in CD45 (E613R) results in hyperre- sponsive thymocytes and B cells on the C57BL/6 background, but no overt autoimmunity, whereas Fas deletion results in a mild autoimmune disease on the same genetic background. In this study, we show that these two mutations cooperate in mice, causing early lethality, autoantibody production, and substantial lymphoproliferation. In double-mutant mice, this phenotype was dependent on both T and B cells. T cell activation required signaling in response to endogenous or commensal antigens, demonstrated by the introduction of a transgenic T cell receptor. Genetic deletion of B cells also prevented T cell activation. Similarly, T cells were necessary for B cell autoantibody production. However, B cells appeared to be intrinsically activated even in the absence of T cells, suggesting that they may drive the phenotype of these mice. These results reveal a requirement for careful control of B cell signaling and cell death in preventing inappropriate lymphocyte activation and autoimmunity.

Original languageEnglish (US)
Pages (from-to)2755-2761
Number of pages7
JournalJournal of Experimental Medicine
Volume205
Issue number12
DOIs
StatePublished - Nov 12 2008
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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