The Juxtamembrane Wedge Negatively Regulates CD45... : Immunity (original) (raw)

The Juxtamembrane Wedge Negatively Regulates CD45 Function in B Cells

• Michelle L. Hermiston
• Allison L. Tan
• Vikas A. Gupta
• Ravindra Majeti
• Arthur Weiss

Immunity

23

(

6

)

:p

635

-

647

,

December 2005

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| DOI: 10.1016/j.immuni.2005.11.001

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.

Copyright © 2005Elsevier, Inc.