| First Author | Cyster JG | Year | 1996 |
| Journal | Nature | Volume | 381 |
| Issue | 6580 | Pages | 325-8 |
| PubMed ID | 8692271 | Mgi Jnum | J:113679 |
| Mgi Id | MGI:3687418 | Doi | 10.1038/381325a0 |
| Citation | Cyster JG, et al. (1996) Regulation of B-lymphocyte negative and positive selection by tyrosine phosphatase CD45. Nature 381(6580):325-8 |
| abstractText | Elimination of self-reactive B cells must be balanced against the need for B-cell diversity for antibody responses to pathogens. To analyse factors that determine the extent of B-cell negative selection, we crossed CD45-deficient mice with mice carrying immunoglobulin transgenes specific for hen egg lysozyme (HEL). CD45 positively regulates antigen-receptor signalling and CD45-deficient HEL-specific B cells gave diminished signalling in response to HEL. Significantly, few mature CD45-/- B cells accumulated, despite normal immature B-cell production. Circulating HEL autoantigen mediates negative selection of mature CD45+/+ HEL-binding B cells but, in striking contrast, the autoantigen positively selected CD45-/- HEL-binding B cells, promoting their accumulation as long-lived IgD(hi) cells. These findings are consistent with a signal-threshold model for B-cell selection and demonstrate that changes in antigen receptor signalling can cause high-affinity self-reactive B cells to be actively retained instead of eliminated, thus revealing a potential mechanism for inherited susceptibility to autoimmune disease. |
