IL-27 directly enhances germinal center b cell activity and potentiates lupus in sanroque mice

Dipti Vijayan, Norhanani Mohd Redzwan, Danielle T. Avery, Rushika C. Wirasinha, Robert Brink, Giles Walters, Stephen Adelstein, Masao Kobayashi, Paul Gray, Michael Elliott, Melanie Wong, Cecile King, Carola G. Vinuesa, Nico Ghilardi, Cindy S. Ma, Stuart G. Tangye, Marcel Batten*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

23 Citations (Scopus)

Abstract

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. Il27ra2/2Roquinsan/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.

Original languageEnglish
Pages (from-to)3008-3017
Number of pages10
JournalJournal of Immunology
Volume197
Issue number8
DOIs
Publication statusPublished - 15 Oct 2016

Fingerprint

Dive into the research topics of 'IL-27 directly enhances germinal center b cell activity and potentiates lupus in sanroque mice'. Together they form a unique fingerprint.

Cite this