Document Detail


Invariant NKT cells inhibit autoreactive B cells in a contact- and CD1d-dependent manner.
MedLine Citation:
PMID:  21209282     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Autoantibody production is a hallmark of autoimmune diseases, such as lupus and rheumatoid arthritis. Accumulating evidence suggests a role of invariant NKT (iNKT) cells in their pathogenesis. Mechanisms underlying the role of iNKT cells in these diseases, however, remain unclear. In this study, we show that iNKT cells suppress IgG anti-DNA Ab and rheumatoid factor production and reduce IL-10-secreting B cells in a contact-dependent manner, but increase total IgG production and enhance activation markers on B cells via soluble factors. In vivo reconstitution with iNKT cells also reduces autoantibody production in iNKT-deficient mice and in SCID mice implanted with B cells. Using an anti-DNA transgenic model, we found that autoreactive B cells spontaneously produce IL-10 and are activated in vivo. In the presence of activated iNKT cells, these autoreactive B cells are selectively reduced, whereas nonautoreactive B cells are markedly activated. Because iNKTs recognize CD1d, we reasoned that CD1d might play a role in the differential regulation of autoreactive versus nonautoreactive B cells by iNKT cells. Indeed, autoreactive B cells express more CD1d than nonautoreactive B cells, and CD1d deficiency in lupus mice exacerbates autoantibody production and enhances Ab response to a self-peptide but not to a foreign peptide. Importantly, iNKT cells fail to inhibit autoantibody production by CD1d-deficient B cells. Thus, iNKT cells inhibit autoreactive B cells in a contact- and CD1d-dependent manner but activate nonautoreactive B cells via cytokines. Such ability of iNKTs to suppress autoantibody production, without causing global suppression of B cells, has important implications for the development of iNKT-based therapy for autoimmune diseases.
Authors:
Jun-Qi Yang; Xiangshu Wen; Peter J Kim; Ram Raj Singh
Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-01-05
Journal Detail:
Title:  Journal of immunology (Baltimore, Md. : 1950)     Volume:  186     ISSN:  1550-6606     ISO Abbreviation:  J. Immunol.     Publication Date:  2011 Feb 
Date Detail:
Created Date:  2011-01-20     Completed Date:  2011-03-07     Revised Date:  2014-09-11    
Medline Journal Info:
Nlm Unique ID:  2985117R     Medline TA:  J Immunol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1512-20     Citation Subset:  AIM; IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Antigens, CD1d / genetics,  metabolism,  physiology*
Autoantibodies / biosynthesis,  metabolism*
B-Lymphocyte Subsets / immunology*,  metabolism*
Cell Adhesion / genetics,  immunology*
Galactosylceramides / pharmacology
Immunoglobulin G / metabolism
Immunosuppressive Agents / pharmacology
Lymphocyte Activation / genetics,  immunology
Lymphocyte Depletion
Mice
Mice, Inbred BALB C
Mice, Inbred NZB
Mice, Knockout
Mice, SCID
Mice, Transgenic
Natural Killer T-Cells / immunology*,  metabolism
Grant Support
ID/Acronym/Agency:
AI80778/AI/NIAID NIH HHS; AR50797/AR/NIAMS NIH HHS; AR56465/AR/NIAMS NIH HHS; R01 AI080778/AI/NIAID NIH HHS; R01 AI080778-01A2/AI/NIAID NIH HHS; R01 AI080778-02/AI/NIAID NIH HHS; R01 AR050797/AR/NIAMS NIH HHS; R01 AR050797-05/AR/NIAMS NIH HHS; R01 AR056465/AR/NIAMS NIH HHS; R01 AR056465-02/AR/NIAMS NIH HHS; R01 AR056465-03/AR/NIAMS NIH HHS
Chemical
Reg. No./Substance:
0/Antigens, CD1d; 0/Autoantibodies; 0/Galactosylceramides; 0/Immunoglobulin G; 0/Immunosuppressive Agents; 0/alpha-galactosylceramide
Comments/Corrections

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