Document Detail


Expansion of autoreactive unresponsive CD21-/low B cells in Sjögren's syndrome-associated lymphoproliferation.
MedLine Citation:
PMID:  23279883     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: Primary Sjögren's syndrome (SS) is an autoimmune disease associated with a high risk of developing non-Hodgkin's lymphoma. This study was undertaken to determine the nature of B cells driving lymphoproliferation in primary SS.
METHODS: B cell subsets and function were analyzed in peripheral blood from 66 adult patients with primary SS (including 14 patients with B cell lymphoproliferative disease [LPD]) and 30 healthy donors, using flow cytometry, calcium mobilization, and gene array analysis. The reactivity of recombinant antibodies isolated from single B cells from patients with primary SS and LPD was tested using an enzyme-linked immunosorbent assay.
RESULTS: We observed an expansion of an unusual CD21-/low B cell population that correlated with lymphoproliferation in patients with primary SS. A majority of CD21-/low B cells from patients with primary SS expressed autoreactive antibodies, which recognized nuclear and cytoplasmic structures. These B cells belonged to the memory compartment, since their Ig genes were mutated. They were unable to induce calcium flux, become activated, or proliferate in response to B cell receptor and/or CD40 triggering, suggesting that these autoreactive B cells may be anergic. However, CD21-/low B cells from patients with primary SS remained responsive to Toll-like receptor (TLR) stimulation. Molecules specifically expressed in CD21-/low B cells that are likely to induce their unresponsive stage were detected in gene array analyses.
CONCLUSION: Patients with primary SS who display high frequencies of autoreactive and unresponsive CD21-/low B cells are susceptible to developing lymphoproliferation. These cells remain in peripheral blood controlled by functional anergy instead of being eliminated, and chronic antigenic stimulation through TLR stimulation may create a favorable environment for breaking tolerance and activating these cells.
Authors:
D Saadoun; B Terrier; J Bannock; T Vazquez; C Massad; I Kang; F Joly; M Rosenzwajg; D Sene; P Benech; L Musset; D Klatzmann; E Meffre; P Cacoub
Related Documents :
24996163 - Stem cells on alert: priming quiescent stem cells after remote injury.
23340483 - Oligodendrogenesis from neural stem cells: perspectives for remyelinating strategies.
24996163 - Stem cells on alert: priming quiescent stem cells after remote injury.
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Arthritis and rheumatism     Volume:  65     ISSN:  1529-0131     ISO Abbreviation:  Arthritis Rheum.     Publication Date:  2013 Apr 
Date Detail:
Created Date:  2013-04-04     Completed Date:  2013-05-22     Revised Date:  2013-07-03    
Medline Journal Info:
Nlm Unique ID:  0370605     Medline TA:  Arthritis Rheum     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1085-96     Citation Subset:  AIM; IM    
Copyright Information:
Copyright © 2013 by the American College of Rheumatology.
Affiliation:
CNRS UMR 7211, INSERM U959, Groupe Hospitalier Pitié-Salpêtrière, and Université Pierre et Marie Curie, Paris 6, Paris, France. david.saadoun@psl.aphp.fr
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Adult
Aged
B-Lymphocyte Subsets / cytology*,  immunology
Calcium / metabolism
Case-Control Studies
Clonal Anergy
Cryoglobulinemia / complications,  genetics,  immunology
Enzyme-Linked Immunosorbent Assay
Female
Flow Cytometry
Gene Expression Profiling
Humans
Lymphoma, B-Cell / complications,  genetics,  immunology
Lymphoproliferative Disorders / genetics,  immunology*
Male
Middle Aged
Oligonucleotide Array Sequence Analysis
RNA, Messenger / analysis
Receptors, Complement 3d / genetics,  metabolism*
Sjogren's Syndrome / genetics,  immunology*
Grant Support
ID/Acronym/Agency:
AI-061093/AI/NIAID NIH HHS; AI-071087/AI/NIAID NIH HHS; AI-082713/AI/NIAID NIH HHS; AI-095848/AI/NIAID NIH HHS; P01 AI061093/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/RNA, Messenger; 0/Receptors, Complement 3d; 7440-70-2/Calcium

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Towards elimination of maternal deaths: maternal deaths surveillance and response.
Next Document:  Impaired Cognitive Function and Reduced Anxiety-Related Behavior in a Promyelocytic Leukemia (PML) T...