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Published Online August 14, 2003
Science DOI: 10.1126/science.1086907

Reports

Submitted on May 16, 2003
Accepted on July 24, 2003

Predominant Autoantibody Production by Early Human B Cell Precursors

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

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

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

During B lymphocyte development, antibodies are assembled by random gene segment re-assortment 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 (55-75%) of all antibodies expressed by early immature B cells displayed self-reactivity, including polyreactive and anti-nuclear specificities (ANAs). Most of these autoantibodies were removed from the population at two discrete checkpoints during B cell development. Inefficient checkpoint regulation would lead to dramatic increases in circulating autoantibodies.


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A. Malaspina, S. Moir, J. Ho, W. Wang, M. L. Howell, M. A. O'Shea, G. A. Roby, C. A. Rehm, J. M. Mican, T.-W. Chun, et al. (2006)
PNAS 103, 2262-2267
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Expansion of Functionally Immature Transitional B Cells Is Associated with Human-Immunodeficient States Characterized by Impaired Humoral Immunity.
A. K. Cuss, D. T. Avery, J. L. Cannons, L. J. Yu, K. E. Nichols, P. J. Shaw, and S. G. Tangye (2006)
J. Immunol. 176, 1506-1516
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Isolation and expression profiling of genes upregulated in bone marrow-derived mononuclear cells of rheumatoid arthritis patients..
N. Nakamura, Y. Shimaoka, T. Tougan, H. Onda, D. Okuzaki, H. Zhao, A. Fujimori, N. Yabuta, I. Nagamori, A. Tanigawa, et al. (2006)
DNA Res 13, 169-183
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