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- Title
B cells drive lymphocyte activation and expansion in mice with the CD45 wedge mutation and Fas deficiency.
- Authors
Gupta, Vikas A; Hermiston, Michelle L; Cassafer, Gail; Daikh, David I; Weiss, Arthur
- Abstract
CD45 and Fas regulate tyrosine phosphorylation and apoptotic signaling pathways, respectively. Mutation of an inhibitory wedge motif in CD45 (E613R) results in hyperresponsive 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.
- Publication
The Journal of experimental medicine, 2008, Vol 205, Issue 12, p2755
- ISSN
1540-9538
- Publication type
Journal Article
- DOI
10.1084/jem.20081204