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

共 50 条

[41]

Radic MZ, 1995, ANN NY ACAD SCI, V764, P384

[42]

RADIC MZ, 1993, J IMMUNOL, V150, P4966

[43] Circulating CD21low B cells in common variable immunodeficiency resemble tissue homing, innate-like B cells [J].

Rakhmanov, Mirzokhid ;

Keller, Baerbel ;

Gutenberger, Sylvia ;

Foerster, Christian ;

Hoenig, Manfred ;

Driessen, Gertjan ;

van der Burg, Mirjam ;

van Dongen, Jacques J. ;

Wiech, Elisabeth ;

Visentini, Marcella ;

Quinti, Isabella ;

Prasse, Antje ;

Voelxen, Nadine ;

Salzer, Ulrich ;

Goldacker, Sigune ;

Fisch, Paul ;

Eibel, Hermann ;

Schwarz, Klaus ;

Peter, Hans-Hartmut ;

Warnatz, Klaus .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2009, 106 (32) :13451-13456

[44] B-CELLS ARE ANERGIC IN TRANSGENIC MICE THAT EXPRESS IGM ANTI-DNA ANTIBODIES [J].

TSAO, BP ;

CHOW, A ;

CHEROUTRE, H ;

SONG, YW ;

MCGRATH, ME ;

KRONENBERG, M .

EUROPEAN JOURNAL OF IMMUNOLOGY, 1993, 23 (09) :2332-2339

[45] Predominant autoantibody production by early human B cell precursors [J].

Wardemann, H ;

Yurasov, S ;

Schaefer, A ;

Young, JW ;

Meffre, E ;

Nussenzweig, MC .

SCIENCE, 2003, 301 (5638) :1374-1377

[46] Expansion of CD19hiCD21lo/neg B cells in common variable immunodeficiency (CVID) patients with autoimmune cytopenia [J].

Warnatz, K ;

Wehr, C ;

Dräger, R ;

Schmidt, S ;

Eibel, H ;

Schlesier, M ;

Peter, HH .

IMMUNOBIOLOGY, 2002, 206 (05) :502-513

[47] Severe deficiency of switched memory B cells (CD27+IgM-IgD-) in subgroups of patients with common variable immunodeficiency:: a new approach to classify a heterogeneous disease [J].

Warnatz, K ;

Denz, A ;

Dräger, R ;

Braun, M ;

Groth, C ;

Wolff-Vorbeck, G ;

Eibel, H ;

Schlesier, M ;

Peter, HH .

BLOOD, 2002, 99 (05) :1544-1551

[48] A new CD21low B cell population in the peripheral blood of patients with SLE [J].

Wehr, C ;

Eibel, H ;

Masilamani, M ;

Illges, H ;

Schlesier, M ;

Peter, HH ;

Warnatz, K .

CLINICAL IMMUNOLOGY, 2004, 113 (02) :161-171

[49] The EUROclass trial: defining subgroups in common variable immunodeficiency [J].

Wehr, Claudia ;

Kivioja, Teemu ;

Schmitt, Christian ;

Ferry, Berne ;

Witte, Torsten ;

Eren, Efrem ;

Vlkova, Marcela ;

Hernandez, Manuel ;

Detkova, Drahomira ;

Bos, Philip R. ;

Poerksen, Gonke ;

von Bemuth, Horst ;

Baumann, Ulrich ;

Goldacker, Sigune ;

Gutenberger, Sylvia ;

Schlesier, Michael ;

Florence, Bergeron-van der Cruyssen ;

Le Garff, Magali ;

Debre, Patrice ;

Jacobs, Roland ;

Jones, John ;

Bateman, Elizabeth ;

Litzman, Jiri ;

van Hagen, P. Martin ;

Plebani, Alessandro ;

Schmidt, Reinhold E. ;

Thon, Vojtech ;

Quinti, Isabella ;

Espanol, Teresa ;

Webster, A. David ;

Chapel, Helen ;

Vihinen, Mauno ;

Oksenhendler, Eric ;

Peter, Hans Hartmut ;

Warnatz, Klaus .

BLOOD, 2008, 111 (01) :77-85

[50] A new population of cells lacking expression of CD27 represents a notable component of the B cell memory compartment in systemic lupus erythematosus [J].

Wei, Chungwen ;

Anolik, Jennifer ;

Cappione, Amedeo ;

Zheng, Bo ;

Pugh-Bernard, Aimee ;

Brooks, James ;

Lee, Eun-Hyung ;

Milner, Eric C. B. ;

Sanz, Inaki .

JOURNAL OF IMMUNOLOGY, 2007, 178 (10) :6624-6633

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