Document Detail


Intrafollicular location of marginal zone/CD1d(hi) B cells is associated with autoimmune pathology in a mouse model of lupus.
MedLine Citation:
PMID:  18607347     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Marginal zone (MZ) B cells contain a large number of autoreactive clones and the expansion of this compartment has been associated with autoimmunity. MZ B cells also efficiently transport blood-borne antigen to the follicles where they activate T cells and differentiate into plasma cells. Using the B6.NZM2410.Sle1.Sle2.Sle3 (B6.TC) model of lupus, we show that the IgM+ CD1d(hi)/MZ B-cell compartment is expanded, and a large number of them reside inside the follicles. Contrary to the peripheral B-cell subset distribution and their activation status, the intrafollicular location of B6.TC IgM+ CD1d(hi)/MZ B cells depends on both bone marrow- and stromal-derived factors. Among the factors responsible for this intrafollicular location, we have identified an increased response to CXCL13 by B6.TC MZ B cells and a decreased expression of VCAM-1 on stromal cells in the B6.TC MZ. However, the reduced number of MZ macrophages observed in B6.TC MZs was independent of the IgM+ CD1d(hi)/B-cell location. B7-2 but not B7-1 deficiency restored IgM+ CD1d(hi)/MZ B-cell follicular exclusion in B6.TC mice, and it correlated with tolerance to dsDNA and a significant reduction of autoimmune pathology. These results suggest that follicular exclusion of IgM+ CD1d(hi)/MZ B cells is an important B-cell tolerance mechanism, and that B7-2 signaling is involved in breaching this tolerance checkpoint.
Authors:
Biyan Duan; Haitao Niu; Zhiwei Xu; Arlene H Sharpe; Byron P Croker; Eric S Sobel; Laurence Morel
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2008-07-07
Journal Detail:
Title:  Laboratory investigation; a journal of technical methods and pathology     Volume:  88     ISSN:  1530-0307     ISO Abbreviation:  Lab. Invest.     Publication Date:  2008 Sep 
Date Detail:
Created Date:  2008-08-26     Completed Date:  2008-09-11     Revised Date:  2013-09-01    
Medline Journal Info:
Nlm Unique ID:  0376617     Medline TA:  Lab Invest     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1008-20     Citation Subset:  IM    
Affiliation:
Department of Pathology, Immunology and Laboratory Medicine, University of Florida College of Medicine, Gainesville, FL 32610-0275, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antigens, CD1 / immunology*
B-Lymphocytes / immunology*
Enzyme-Linked Immunosorbent Assay
Flow Cytometry
Fluorescent Antibody Technique
Lupus Erythematosus, Systemic / immunology*
Mice
Mice, Inbred C57BL
Grant Support
ID/Acronym/Agency:
K01 AR056725/AR/NIAMS NIH HHS; R01 AI058150/AI/NIAID NIH HHS; R01 AI068965/AI/NIAID NIH HHS; R01-AI058150/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/Antigens, CD1
Comments/Corrections

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