| First Author | Kench JA | Year | 1998 |
| Journal | J Exp Med | Volume | 188 |
| Issue | 5 | Pages | 909-17 |
| PubMed ID | 9730892 | Mgi Jnum | J:50289 |
| Mgi Id | MGI:1298142 | Doi | 10.1084/jem.188.5.909 |
| Citation | Kench JA, et al. (1998) Efficient peripheral clonal elimination of B lymphocytes in MRL/lpr mice bearing autoantibody transgenes. J Exp Med 188(5):909-17 |
| abstractText | Peripheral B cell tolerance was studied in mice of the autoimmune-prone, Fas-deficient MRL/lpr.H-2(d) genetic background by introducing a transgene that directs expression of membrane-bound H-2K(b) antigen to liver and kidney (MT-K-b) and a second transgene encoding antibody reactive with this antigen (3-83 mu delta, anti-K-k,K-b). Control immunoglobulin transgenic (Ig-Tg) MRL/lpr.H-2(d) mice lacking the K-b antigen had large numbers of splenic and lymph node B cells bearing the transgene-encoded specificity, whereas B cells of the double transgenic (Dbl- Tg) MRL/lpr.H-2(d) mice were deleted as efficiently as in Dbl-Tg mice of a nonautoimmune B10.D2 genetic background. In spite of the severely restricted peripheral B cell repertoire of the Ig-Tg MRL/lpr.H-2(d) mice, and notwithstanding deletion of the autospecific B cell population in the Dbl-Tg MRL/lpr.H-2(d) mice, both types of mice developed lymphoproliferation and exhibited elevated levels of IgG anti-chromatin autoantibodies. Interestingly, Dbl-Tg MRL/lpr.H-2(d) mice had a shorter lifespan than Ig-Tg MRL/lpr.H-2(d) mice, apparently as an indirect result of their relative B cell lymphopenia. These data suggest that in MRL/lpr mice peripheral B cell tolerance is not globally defective, but that certain B cells with receptors specific for nuclear antigens are regulated differently than are cells reactive to membrane autoantigens. |
