| First Author | Arkatkar T | Year | 2017 |
| Journal | J Exp Med | Volume | 214 |
| Issue | 11 | Pages | 3207-3217 |
| PubMed ID | 28899868 | Mgi Jnum | J:251559 |
| Mgi Id | MGI:5924900 | Doi | 10.1084/jem.20170580 |
| Citation | Arkatkar T, et al. (2017) B cell-derived IL-6 initiates spontaneous germinal center formation during systemic autoimmunity. J Exp Med 214(11):3207-3217 |
| abstractText | Recent studies have identified critical roles for B cells in triggering autoimmune germinal centers (GCs) in systemic lupus erythematosus (SLE) and other disorders. The mechanisms whereby B cells facilitate loss of T cell tolerance, however, remain incompletely defined. Activated B cells produce interleukin 6 (IL-6), a proinflammatory cytokine that promotes T follicular helper (TFH) cell differentiation. Although B cell IL-6 production correlates with disease severity in humoral autoimmunity, whether B cell-derived IL-6 is required to trigger autoimmune GCs has not, to our knowledge, been addressed. Here, we report the unexpected finding that a lack of B cell-derived IL-6 abrogates spontaneous GC formation in mouse SLE, resulting in loss of class-switched autoantibodies and protection from systemic autoimmunity. Mechanistically, B cell IL-6 production was enhanced by IFN-gamma, consistent with the critical roles for B cell-intrinsic IFN-gamma receptor signals in driving autoimmune GC formation. Together, these findings identify a key mechanism whereby B cells drive autoimmunity via local IL-6 production required for TFH differentiation and autoimmune GC formation. |
