Complement receptor 2/CD21- human naive B cells contain mostly autoreactive unresponsive clones.
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.
Laboratory of Molecular Immunology, Hospital for Special Surgery, New York, NY, USA.
Isabelle
I
Isnardi
Yen-Shing
YS
Ng
Laurence
L
Menard
Greta
G
Meyers
David
D
Saadoun
Iva
I
Srdanovic
Jonathan
J
Samuels
Jessica
J
Berman
Jane H
JH
Buckner
Charlotte
C
Cunningham-Rundles
Eric
E
Meffre
D000328:Adult; D015703:Antigens, CD / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology; D017209:Apoptosis / Q000276:immunology; D001323:Autoantibodies / Q000276:immunology; D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology*; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D015415:Biomarkers; D019013:CD40 Antigens / Q000276:immunology; D002455:Cell Division / Q000276:immunology; D017635:Clonal Anergy / Q000235:genetics / Q000276:immunology*; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D016130:Immunophenotyping; D060945:Inducible T-Cell Co-Stimulator Ligand; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology; D037181:Lectins, C-Type / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D017464:Receptors, Complement 3d / Q000235:genetics* / Q000276:immunology*; D017455:Receptors, IgE / Q000276:immunology; D053303:Transmembrane Activator and CAML Interactor Protein / Q000276:immunology; D055815:Young Adult; D000099192:CD69 Antigens
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D001323:Autoantibodies; D015415:Biomarkers; D019013:CD40 Antigens; D060945:Inducible T-Cell Co-Stimulator Ligand; D053645:Interleukin-2 Receptor alpha Subunit; D037181:Lectins, C-Type; D017464:Receptors, Complement 3d; D017455:Receptors, IgE; D053303:Transmembrane Activator and CAML Interactor Protein; D000099192:CD69 Antigens; C498514:ICOSLG protein, human; C508017:IL2RA protein, human; C108467:TNFRSF13B protein, human