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Science 301 (5638): 1374-1377

Copyright © 2003 by the American Association for the Advancement of Science

Predominant Autoantibody Production by Early Human B Cell Precursors

Hedda Wardemann,1 Sergey Yurasov,1,3 Anne Schaefer,1 James W. Young,4 Eric Meffre,1,5* Michel C. Nussenzweig1,2*

Abstract: During B lymphocyte development, antibodies are assembled by random gene segment reassortment to produce a vast number of specificities. A potential disadvantage of this process is that some of the antibodies produced are self-reactive. We determined the prevalence of self-reactive antibody formation and its regulation in human B cells. A majority (55 to 75%) of all antibodies expressed by early immature B cells displayed self-reactivity, including polyreactive and anti-nuclear specificities. Most of these autoantibodies were removed from the population at two discrete checkpoints during B cell development. Inefficient checkpoint regulation would lead to substantial increases in circulating autoantibodies.

1 Laboratory of Molecular Immunology, Rockefeller University, New York, NY 10021, USA.
2 Howard Hughes Medical Institute, Rockefeller University, New York, NY 10021, USA.
3 Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
4 Allogeneic Bone Marrow Transplant and Clinical Immunology Services, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
5 Hospital for Special Surgery, Weill Medical College of Cornell University, New York, NY 10021, USA.

* To whom correspondence should be addressed. E-mail: meffree{at}, nussen{at}

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J. Immunol. 186, 6338-6344
   Abstract »    Full Text »    PDF »
Tolerance Induction of IgG+ Memory B Cells by T Cell-Independent Type II Antigens.
K. Haniuda, T. Nojima, K. Ohyama, and D. Kitamura (2011)
J. Immunol. 186, 5620-5628
   Abstract »    Full Text »    PDF »
Interference by antiruthenium antibodies in the Roche thyroid-stimulating hormone assay.
M. M. Buijs, J. P. M. C. Gorgels, and E. Endert (2011)
Annals of Clinical Biochemistry 48, 276-281
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Alternative mechanisms of receptor editing in autoreactive B cells.
O. Kalinina, C. M. Doyle-Cooper, J. Miksanek, W. Meng, E. L. Prak, and M. G. Weigert (2011)
PNAS 108, 7125-7130
   Abstract »    Full Text »    PDF »
Anergic Responses Characterize a Large Fraction of Human Autoreactive Naive B Cells Expressing Low Levels of Surface IgM.
T. D. Quach, N. Manjarrez-Orduno, D. G. Adlowitz, L. Silver, H. Yang, C. Wei, E. C. B. Milner, and I. Sanz (2011)
J. Immunol. 186, 4640-4648
   Abstract »    Full Text »    PDF »
Increased Expression of B Cell Activation Factor Supports the Abnormal Expansion of Transitional B Cells in Systemic Lupus Erythematosus.
J Rheumatol 38, 642-651
   Abstract »    Full Text »    PDF »
Determinism and stochasticity during maturation of the zebrafish antibody repertoire.
N. Jiang, J. A. Weinstein, L. Penland, R. A. White III, D. S. Fisher, and S. R. Quake (2011)
PNAS 108, 5348-5353
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