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Infection and Immunity, June 2004, p. 3515-3523, Vol. 72, No. 6
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.6.3515-3523.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Specific In Vivo Deletion of B-Cell Subpopulations Expressing Human Immunoglobulins by the B-Cell Superantigen Protein L

Muriel Viau,1 Nancy S. Longo,2 Peter E. Lipsky,2 Lars Björck,3 and Moncef Zouali1*

Institut National de Sante et de Recherche Medicale (INSERM U 430), Immunopathologie Humaine, 75006 Paris, France,1 National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, Maryland 20892-1820,2 Department of Cell and Molecular Biology, Lund University, SE-22184 Lund, Sweden3

Received 3 December 2003/ Returned for modification 24 January 2004/ Accepted 23 February 2004

Some pathogens have evolved to produce proteins, called B-cell superantigens, that can interact with human immunoglobulin variable regions, independently of the combining site, and activate B lymphocytes that express the target immunoglobulins. However, the in vivo consequences of these interactions on human B-cell numbers and function are largely unknown. Using transgenic mice expressing fully human immunoglobulins, we studied the consequences of in vivo exposure of protein L of Peptostreptococcus magnus with human immunoglobulins. In the mature pool of B cells, protein L exposure resulted in a specific reduction of splenic marginal-zone B cells and peritoneal B-1 cells. Splenic B cells exhibited a skewed light-chain repertoire consistent with the capacity of protein L to bind specific kappa gene products. Remarkably, these two B-cell subsets are implicated in innate B-cell immunity, allowing rapid clearance of pathogens. Thus, the present study reveals a novel mechanism that may be used by some infectious agents to subvert a first line of the host's immune defense.

* Corresponding author. Mailing address: Immunopathologie Humaine, INSERM U430, 15 rue de l'Ecole de Médecine, 75006 Paris, France. Phone: 33-1-55-42-82-64. Fax: 33-1-45-84-79-62. E-mail: moncef.zouali{at}wanadoo.fr.

Editor: F. C. Fang

Infection and Immunity, June 2004, p. 3515-3523, Vol. 72, No. 6
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.6.3515-3523.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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