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

被引：370

作者：

Isnardi, Isabelle ^{[1
]}

Ng, Yen-Shing ^{[1
]}

Menard, Laurence ^{[1
]}

Meyers, Greta ^{[1
]}

Saadoun, David ^{[1
]}

Srdanovic, Iva ^{[1
]}

Samuels, Jonathan ^{[1
]}

Berman, Jessica ^{[2
]}

Buckner, Jane H. ^{[3
]}

Cunningham-Rundles, Charlotte ^{[4
]}

Meffre, Eric ^{[1
]}

机构：

[1] Hosp Special Surg, Lab Mol Immunol, New York, NY 10021 USA

[2] Hosp Special Surg, Div Rheumatol, New York, NY 10021 USA

[3] Benaroya Res Inst, Translat Res Program, Seattle, WA USA

[4] Mt Sinai Med Ctr, Dept Med & Pediat, New York, NY 10029 USA

来源：

BLOOD | 2010年 / 115卷 / 24期

基金：

美国国家卫生研究院;

关键词：

COMMON VARIABLE IMMUNODEFICIENCY; SYSTEMIC-LUPUS-ERYTHEMATOSUS; ANTI-DNA ANTIBODIES; LYMPHOCYTES-B; SIGNAL-TRANSDUCTION; TRANSGENIC MICE; SELF-TOLERANCE; EXPRESSION; ANERGY; POPULATION;

D O I：

10.1182/blood-2009-09-243071

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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. (Blood. 2010;115(24):5026-5036)

引用

页码：5026 / 5036

页数：11

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