The Journal of Experimental Medicine
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Published online 29 December 2003 doi:10.1084/jem.20031550
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 199, Number 1, 145-150
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Brief Definitive Report

 Surrogate Light Chain Expressing Human Peripheral B Cells Produce Self-reactive Antibodies

Eric Meffre1,5, Anne Schaefer1, Hedda Wardemann1, Patrick Wilson1,4, Eric Davis3 and Michel C. Nussenzweig1,2

1 Laboratory of Molecular Immunology, The Rockefeller University
2 Howard Hughes Medical Institute, New York, NY 10021
3 Division of Clinical Sciences, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892
4 Oklahoma Medical Research Foundation, Oklahoma City, OK 73104
5 Hospital for Special Surgery and Weill Medical College of Cornell University, New York, NY 10021

Address correspondence to Eric Meffre, The Hospital for Surgery, 535 E. 70th St., New York, NY 10021. Phone: (212) 774-2347; Fax: (212) 717-1192; email: meffree{at}hss.edu; or Michel C. Nussenzweig, The Rockefeller University, 1230 York Ave., New York, NY 10021. Phone: (212) 327-8067; Fax: (212) 327-8370; email: nussen{at}mail.rockefeller.edu

Human B cells that coexpress surrogate and conventional light chains (V-preB+L+) show an unusual heavy and light chain antibody repertoire that display evidence of receptor editing. However, it is unclear whether V-preB+L+ B cells have been silenced by receptor editing or still express autoreactive antibodies. Here we report that 68% of the antibodies expressed by V-preB+L+ B cells are autoreactive. A majority of these autoantibodies are true antinuclear antibodies (ANA), and 50% of the ANAs are also reactive with a diverse group of antigens that include dsDNA, ssDNA, immunoglobulin, insulin, and bacterial lipopolysaccharide. Such antibodies are rarely encountered among conventional B cells. We conclude that V-preB+L+ B cells are a unique subset of normal circulating human B cells that escape central tolerance mechanisms and express self-reactive antibodies including potentially harmful ANAs.

Key Words: surrogate light chains • B lymphocytes • poly • reactive • autoantibody

The online version of this article includes supplemental material.


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