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PMID: 20231422 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

Complement receptor 2/CD21- human naive B cells contain mostly autoreactive unresponsive clones.

Blood ·Vol. 115 ·No. 24 ·2010-06-17 ·Pages 5026-36

Isnardi I, Ng YS, Menard L, Meyers G, Saadoun D, Srdanovic I, Samuels J, Berman J, Buckner JH, Cunningham-Rundles C, Meffre E

Abstract

Complement receptor 2-negative (CR2/CD21(-)) B cells have been found enriched in patients with autoimmune diseases and in common variable immunodeficiency (CVID) patients who are prone to autoimmunity. However, the physiology of CD21(-/lo) B cells remains poorly characterized. We found that some rheumatoid arthritis (RA) patients also display an increased frequency of CD21(-/lo) B cells in their blood. A majority of CD21(-/lo) B cells from RA and CVID patients expressed germline autoreactive antibodies, which recognized nuclear and cytoplasmic structures. In addition, these B cells 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. Moreover, gene array analyses of CD21(-/lo) B cells revealed molecules specifically expressed in these B cells and that are likely to induce their unresponsive stage. Thus, CD21(-/lo) B cells contain mostly autoreactive unresponsive clones, which express a specific set of molecules that may represent new biomarkers to identify anergic B cells in humans.

MeSH Terms
Adult Antigens, CD/immunology Antigens, Differentiation, T-Lymphocyte/immunology Apoptosis/immunology Autoantibodies/immunology Autoimmune Diseases/genetics,immunology B-Lymphocytes/cytology,immunology Biomarkers CD40 Antigens/immunology Cell Division/immunology Clonal Anergy/genetics,immunology Female Gene Expression Profiling Humans Immunophenotyping Inducible T-Cell Co-Stimulator Ligand Interleukin-2 Receptor alpha Subunit/immunology Lectins, C-Type/immunology Lymphocyte Activation/immunology Male Receptors, Complement 3d/genetics,immunology Receptors, IgE/immunology Transmembrane Activator and CAML Interactor Protein/immunology Young Adult
Chemicals
Antigens, CD Antigens, Differentiation, T-Lymphocyte Autoantibodies Biomarkers CD40 Antigens CD69 antigen ICOSLG protein, human IL2RA protein, human Inducible T-Cell Co-Stimulator Ligand Interleukin-2 Receptor alpha Subunit Lectins, C-Type Receptors, Complement 3d Receptors, IgE TNFRSF13B protein, human Transmembrane Activator and CAML Interactor Protein
Authors & Affiliations
11 authors, click to expand affiliations / ORCID
Isnardi Isabelle
Laboratory of Molecular Immunology, Hospital for Special Surgery, New York, NY, USA.
Ng Yen-Shing
Menard Laurence
Meyers Greta
Saadoun David
Srdanovic Iva
Samuels Jonathan
Berman Jessica
Buckner Jane H
Cunningham-Rundles Charlotte
Meffre Eric
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Article Info
Journal
Blood
Abbr.
Blood
ISSN
1528-0020
DOI
10.1182/blood-2009-09-243071
Published
2010-06-17
Epub
2010-00-15
Pages
5026-36
Language
English
Region
United States
NLM ID
7603509
PMCID
PMC3373152
Subset
IM
Grants
NIAID NIH HHS · R01 AI071087 · United States
NIAID NIH HHS · AI071087 · United States
NIAID NIH HHS · P01 AI061093 · United States
NIAID NIH HHS · T32 AI089704 · United States
NIAID NIH HHS · R21 AI095848 · United States
NIAID NIH HHS · AI061093 · United States
Corrections
CommentIn
PMID: 20558622
CommentIn
PMID: 21051568
External Links
PubMed source DOI: 10.1182/blood-2009-09-243071 PMC Full Text View journal details
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