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International Immunology, Vol. 14, No. 1, 45-54, January 2002
© 2002 Japanese Society for Immunology

Persistence of partially functional double-stranded (ds) DNA binding B cells in mice transgenic for the IgM heavy chain of an anti-dsDNA antibody

Yih-Pai Chu, Devon Taylor1, Han-Guang Yan2, Betty Diamond and Linda Spatz2

Departments of Microbiology & Immunology and Medicine, Albert Einstein College of Medicine, Bronx, NY 10461, USA
1 Department of Chemistry, and
2 Department of Microbiology and Immunology, Sophie Davis School of Biomedical Education, City College of New York, New York, NY 10031, USA

Correspondence to: L. Spatz

One mechanism by which anti-double stranded (ds) DNA B cells are regulated is anergy. Multiple phenotypes have been attributed to anergic B cells in various transgenic models. Differences in the nature of the antigen and in the avidity of antigen–antibody interactions may account for these variations in phenotype. In the present study we describe a population of dsDNA binding B cells that display many of the features of anergic B cells, but have characteristics which suggest they are partially functional as well. These B cells do not spontaneously secrete antibody nor can they be induced to secrete antibody following receptor cross-linking in vitro. Furthermore, they display an immature phenotype and have a shortened lifespan, characteristic of anergic B cells. However, they can be induced to secrete anti-dsDNA antibody following activation with T cell-derived factors as well as with lipopolysaccharide (LPS) and they can be recovered by somatic cell hybridization even in the absence of LPS stimulation prior to fusion. These results suggest that antigen receptor signaling can be uncoupled from signaling induced by T cell-derived factors or LPS and that this may be a mechanism for maintaining tolerance. This may have protective advantages because it may enable B cells to be down-regulated in response to autoantigen yet be available for recruitment in an inflammatory response.

Keywords: anergy, double-stranded DNA, systemic lupus erythematosus, tolerance

The first two authors contributed equally to this work

Transmitting editor: J. V. Ravetch


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