Invariant NKT cells limit activation of autoreactive CD1d-positive B cells

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Published May 3, 2010
The Rockefeller University Press, doi: 10.1084/jem.20091314
© 2010 Wermeling et al.
Brief Definitive Report
Invariant NKT cells limit activation of autoreactive CD1d-positive B cells
Fredrik Wermeling1, Sara M. Lind1, Emilie Domange Jordö1, Susanna L. Cardell2, and Mikael C.I. Karlsson1
+ Author Affiliations

1Department of Medicine, Karolinska Institutet, 171 76 Stockholm, Sweden
2Department of Microbiology and Immunology, Göteborg University, 405 30 Göteborg, Sweden
CORRESPONDENCE Mikael C.I. Karlsson: Mikael.Karlsson@ki.se

Abstract
Faulty activation of autoreactive B cells is a hallmark of autoimmune diseases like systemic lupus erythematosus (SLE). An important feature restricting activation of autoreactive B cells is efficient removal of apoptotic material. Mounting evidence also connects a primary defect in invariant natural killer T (iNKT) cells to autoimmune disease development. However, exactly how this unconventional T cell subset is involved remains to be defined. Here, we identify a suppressive role for iNKT cells in a model where autoantibody production is triggered by an increased load of circulating apoptotic cells, resembling the situation in SLE patients. Absence or reduction of iNKT cells as well as absence of CD1d-expression on B cells, needed for direct iNKT–B cell interaction, leads to increased autoreactive B cell activation and symptoms of disease. The suppression mediated by the iNKT cells is observed before B cell entry into germinal centers and can be rescued by transferring iNKT cells to deficient mice. This links iNKT cells to handling of dying cells and identifies a novel peripheral tolerance checkpoint relevant for autoimmune disease. Thus, these observations connect two clinical observations in SLE patients previously considered to be unrelated and define a new target for immunotherapy.

Footnotes

Abbreviations used: αGalCer α-galactosylceramide
FoB follicular B cell
GC germinal center
IC immune complex
iNKT invariant natural killer T cell
MZB marginal zone B cell
PI preimmune
SLE systemic lupus erythematosus

Submitted: 16 June 2009 Accepted: 11 March 2010 This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).

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