| First Author | Hermiston ML | Year | 2005 |
| Journal | Immunity | Volume | 23 |
| Issue | 6 | Pages | 635-47 |
| PubMed ID | 16356861 | Mgi Jnum | J:113310 |
| Mgi Id | MGI:3665378 | Doi | 10.1016/j.immuni.2005.11.001 |
| Citation | Hermiston ML, et al. (2005) The juxtamembrane wedge negatively regulates CD45 function in B cells. Immunity 23(6):635-47 |
| abstractText | 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. |
