| First Author | Liu Y | Year | 2017 |
| Journal | Arthritis Res Ther | Volume | 19 |
| Issue | 1 | Pages | 225 |
| PubMed ID | 28982388 | Mgi Jnum | J:261352 |
| Mgi Id | MGI:6155313 | Doi | 10.1186/s13075-017-1438-2 |
| Citation | Liu Y, et al. (2017) T-bet(+)CD11c(+) B cells are critical for antichromatin immunoglobulin G production in the development of lupus. Arthritis Res Ther 19(1):225 |
| abstractText | BACKGROUND: A hallmark of systemic lupus erythematosus is high titers of circulating autoantibodies. Recently, a novel CD11c(+) B-cell subset has been identified that is critical for the development of autoimmunity. However, the role of CD11c(+) B cells in the development of lupus is unclear. Chronic graft-versus-host disease (cGVHD) is a lupus-like syndrome with high autoantibody production. The purpose of this study was to explore the role of CD11c(+) B cells in the pathogenesis of lupus in cGVHD mice. METHODS: cGVHD was induced by an intraperitoneal injection of 5 x 10(7) Bm12 splenocytes into B6 mice. Flow cytometry was used to analyze mice splenocytes and human samples. Magnetic beads were used to isolate mice B cells. Gene expression was determined by real-time quantitative polymerase chain reaction (RT-qPCR). Enzyme-linked immunosorbent assay (ELISA) was used to detect antibodies in serum and supernatants. RESULTS: The percentage and absolute number of CD11c(+) B cells was increased in cGVHD-induced lupus, with elevated levels of antichromatin immunoglobulin (Ig)G and IgG2a in sera. CD11c(+) plasma cells from cGVHD mice produced large amounts of antichromatin IgG2a upon stimulation. Depletion of CD11c(+) B cells reduced antichromatin IgG and IgG2a production. T-bet was upregulated in CD11c(+) B cells. Knockout of T-bet in B cells alleviated cGVHD-induced lupus. Importantly, the percentage of T-bet(+)CD11c(+) B cells increased in lupus patients and positively correlated with serum antichromatin levels. CONCLUSION: T-bet(+)CD11c(+) B cells promoted high antichromatin IgG production in the lupus-like disease model cGVHD. In lupus patients, the percentage of T-bet(+)CD11c(+) B cells was elevated and positively correlated with antichromatin antibodies. The findings provide potential therapeutic insight into lupus disease treatment. |
