IL-27 Directly Enhances Germinal Center B Cell Activity and Potentiates Lupus in Sanroque Mice
Germinal centers (GC) give rise to high-affinity and long-lived Abs and are critical in immunity and autoimmunity. IL-27 supports GCs by promoting survival and function of T follicular helper cells. We demonstrate that IL-27 also directly enhances GC B cell function. Exposure of naive human B cells to rIL-27 during in vitro activation enhanced their differentiation into CD20+CD38+CD27lowCD95+CD10+ cells, consistent with the surface marker phenotype of GC B cells. This effect was inhibited by loss-of-function mutations in STAT1 but not STAT3 To extend these findings, we studied the in vivo effects of IL-27 signals to B cells in the GC-driven Roquinsan/san lupus mouse model. Il27ra-/-Roquinsan/san mice exhibited significantly reduced GCs, IgG2a(c)+ autoantibodies, and nephritis. Mixed bone marrow chimeras confirmed that IL-27 acts through B cell- and CD4+ T cell-intrinsic mechanisms to support GCs and alter the production of pathogenic Ig isotypes. To our knowledge, our data provide the first evidence that IL-27 signals directly to B cells promote GCs and support the role of IL-27 in lupus.
|Authors||Vijayan, D.; Mohd Redzwan, N.; Avery, D. T.; Wirasinha, R. C.; Brink, R.; Walters, G.; Adelstein, S.; Kobayashi, M.; Gray, P.; Elliott, M.; Wong, M.; King, C.; Vinuesa, C. G.; Ghilardi, N.; Ma, C. S.; Tangye, S. G.; Batten, M.;|
|Publisher Name||JOURNAL OF IMMUNOLOGY|
|URL link to publisher's version||http://www.ncbi.nlm.nih.gov/pubmed/27619997|
|OpenAccess link to author's accepted manuscript version||https://publications.gimr.garvan.org.au/open-access/13428|