Immunity
Volume 23, Issue 6, December 2005, Pages 635-647
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Article
The Juxtamembrane Wedge Negatively Regulates CD45 Function in B Cells

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Summary

CD45 is a receptor-like protein tyrosine phosphatase highly expressed on all nucleated hematopoietic cells. We previously generated mice containing a point mutation in the juxtamembrane wedge of CD45. Demonstrating the critical negative regulatory function of the wedge, the CD45 E613R mutation led to a lymphoproliferative disorder (LPD) and a lupus-like autoimmune syndrome. Here we show the central role of B cells in this phenotype. Genetic elimination of B cells, but not T cells, ablates the LPD. In contrast to CD45-deficient B cells, the E613R mutation generates hyperresponsive B cells. Comparison of CD45-deficient and CD45 E613R mice reveals dichotomous effects of these mutations on B cell development. Together, the results support a role for CD45 as a rheostat, with both positive and negative regulatory functions, that fine-tunes the signal transduction threshold at multiple checkpoints in B cell development.

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Present address: Department of Medicine, Stanford University, Palo Alto, California 94305.