| First Author | Ahuja A | Year | 2007 |
| Journal | J Immunol | Volume | 179 |
| Issue | 5 | Pages | 3351-61 |
| PubMed ID | 17709552 | Mgi Jnum | J:151822 |
| Mgi Id | MGI:4355309 | Doi | 10.4049/jimmunol.179.5.3351 |
| Citation | Ahuja A, et al. (2007) Depletion of B cells in murine lupus: efficacy and resistance. J Immunol 179(5):3351-61 |
| abstractText | In mice, genetic deletion of B cells strongly suppresses systemic autoimmunity, providing a rationale for depleting B cells to treat autoimmunity. In fact, B cell depletion with rituximab is approved for rheumatoid arthritis patients, and clinical trials are underway for systemic lupus erythematosus. Yet, basic questions concerning mechanism, pathologic effect, and extent of B cell depletion cannot be easily studied in humans. To better understand how B cell depletion affects autoimmunity, we have generated a transgenic mouse expressing human CD20 on B cells in an autoimmune-prone MRL/MpJ-Fas(lpr) (MRL/lpr) background. Using high doses of a murine anti-human CD20 mAb, we were able to achieve significant depletion of B cells, which in turn markedly ameliorated clinical and histologic disease as well as antinuclear Ab and serum autoantibody levels. However, we also found that B cells were quite refractory to depletion in autoimmune-prone strains compared with non-autoimmune-prone strains. This was true with multiple anti-CD20 Abs, including a new anti-mouse CD20 Ab, and in several different autoimmune-prone strains. Thus, whereas successful B cell depletion is a promising therapy for lupus, at least some patients might be resistant to the therapy as a byproduct of the autoimmune condition itself. |
