| First Author | Ju ZL | Year | 2007 |
| Journal | Immunology | Volume | 120 |
| Issue | 2 | Pages | 281-9 |
| PubMed ID | 17073941 | Mgi Jnum | J:122315 |
| Mgi Id | MGI:3713987 | Doi | 10.1111/j.1365-2567.2006.02500.x |
| Citation | Ju ZL, et al. (2007) Unexpected development of autoimmunity in BAFF-R-mutant MRL-lpr mice. Immunology 120(2):281-9 |
| abstractText | BAFF-R is the predominant receptor that mediates B-cell activating factor (BAFF)-dependent B-cell signalling and plays a critical role in late-stage B-cell maturation and survival. BAFF has been implicated in the development of autoimmunity and systemic lupus erythematosus (SLE). To define the role of BAFF-R in autoimmunity and SLE, we crossed A/WySnJ mice with MRL-lpr mice and generated BAFF-R-mutant MRL-lpr mice. The BAFF-R mutation markedly impaired the development of immature, mature and marginal zone B cells in the spleens of MRL-lpr mice. Unexpectedly, the BAFF-R mutation in MRL-lpr mice did not result in decreased autoantibody production, hypergammaglobulinaemia or immune complex-mediated glomerulonephritis. Rather, the ability of BAFF-R-mutant lpr splenic B cells to produce immunoglobulins in vitro was not decreased, although germinal centre formation, antibody response and B-cell proliferation were impaired. Further studies found increased numbers of B cells in the bone marrow of BAFF-R-mutant MRL-lpr mice compared to the BAFF-R-intact lupus mice. ELISPOT analysis revealed that BAFF-R-mutant MRL-lpr mice had more antibody-secreting cells in their bone marrow than the control mice. Thus, these findings could explain the development of autoimmunity and hypergammaglobulinaemia observed in BAFF-R-mutant MRL-lpr mice. |
