Journal article
NFκB1 is essential to prevent the development of multiorgan autoimmunity by limiting IL-6 production in follicular B cells
E de Valle, G Grigoriadis, LA O'Reilly, SN Willis, MJ Maxwell, LM Corcoran, E Tsantikos, JKS Cornish, KA Fairfax, A Vasanthakumar, MA Febbraio, ML Hibbs, M Pellegrini, A Banerjee, PD Hodgkin, A Kallies, F Mackay, A Strasser, S Gerondakis, R Gugasyan
Journal of Experimental Medicine | Published : 2016
DOI: 10.1084/jem.20151182
Abstract
We examined the role of NFκB1 in the homeostasis and function of peripheral follicular (Fo) B cells. Aging mice lacking NFκB1 (Nfκb1-/-) develop lymphoproliferative and multiorgan autoimmune disease attributed in large part to the deregulated activity of Nfκb1-/- Fo B cells that produce excessive levels of the proinflammatory cytokine interleukin 6 (IL-6). Despite enhanced germinal center (GC) B cell differentiation, the formation of GC structures was severely disrupted in the Nfκb1-/- mice. Bone marrow chimeric mice revealed that the Fo B cell-intrinsic loss of NFκB1 led to the spontaneous generation of GC B cells. This was primarily the result of an increase in IL-6 levels, which promotes ..
View full abstractGrants
Awarded by National Science Foundation
Funding Acknowledgements
This work was funded by the National Health and Medical Research Council (NHMRC) of Australia as follows: a fellowship to A. Strasser (1020363); a program grant to A. Strasser (1016701); and project grants to LA. O'Reilly (1009145), M.L. Hibbs (1008288), A. Strasser (1046010), and R. Gugasyan (603713). E. de Valle is a recipient of an Australian Postgraduate Award. G. Grigoriadis is supported by a Haematology Society of Australia and New Zealand (HSANZ) New/Young Investigator Award and is a Victorian Cancer Agency Clinical Research fellow. A. Kallies is supported by the Sylvia and Charles Viertel Foundation. We gratefully acknowledge the Victorian Operational Infrastructure Support Program and an NHMRC infrastructure grant.