| First Author | Cyster JG | Year | 1995 |
| Journal | Immunity | Volume | 2 |
| Issue | 1 | Pages | 13-24 |
| PubMed ID | 7600299 | Mgi Jnum | J:28348 |
| Mgi Id | MGI:75966 | Doi | 10.1016/1074-7613(95)90075-6 |
| Citation | Cyster JG, et al. (1995) Protein tyrosine phosphatase 1C negatively regulates antigen receptor signaling in B lymphocytes and determines thresholds for negative selection. Immunity 2(1):13-24 |
| abstractText | Motheaten viable (mev) mice are deficient in the cytosolic protein tyrosine phosphatase, PTP1C, and exhibit severe B cell immunodeficiency and autoantibody production. The role of PTP1C in B cell selection and function was analyzed by breeding immunoglobulin transgenes specific for a defined antigen, hen egg lysozyme, into mev mice. Antigen triggered a greater and more rapid elevation of intracellular calcium in PTP1C-deficient B cells, indicating that this phosphatase negatively regulates immunoglobulin signaling. Elimination of self-reactive B cells carrying this signal-enhancing mutation was triggered during their development by binding a lower valency form of self-antigen than is normally required. These findings establish that activation of distinct repertoire-censoring mechanisms depends on quantitative differences in antigen receptor signaling, whose thresholds are determined by negative regulation through PTP1C. |
