The Journal of Immunology, 2007, 178: B95.
Copyright © 2007 by The American Association of Immunologists, Inc.
Mature B cells from healthy people which are permanently class switched to the IgD isotype are autoreactive
Kristi A Koelsch1,2,
Nai-Ying Zheng1,
Qingzhao Zhang1,2,
Andrew Duty1,3,
Leni A. Abraham1,
Christina Helms1,
Melissa D. Mathias1,
Mathew Jared1,
Kenneth Smith1 and
Patrick C. Wilson1,2
1 Molecular Immunogenetics Program, Oklahoma Medical Research Foundation, 825 N.E. 13th Street, Oklahoma City, Oklahoma, 73104,
2 Department of Pathology,
3 Department of Microbiology, University of Oklahoma Health Sciences Center, 940 Stanton L. Young Boulevard, Oklahoma City, Oklahoma, 73104
Abstract
Determining the origin and fate of autoreactive B cells is critical to understanding and treating autoimmune diseases. We report that compared to antibodies from naïve and IgG memory B cells those from cells that have class switched to IgD via genetic recombination (C
-CS) are highly reactive with self-antigens, despite being derived from healthy people. Half of the antibodies from C-CS B cells bind various autoantigens, and they are frequently polyreactive. Many also bind HEp-2 antigens. Intriguingly, some C-CS B cells have accumulated residues in the variable regions that mediate anti-DNA reactivity via somatic hypermutation and selection, suggesting an immunological origin for anti-DNA antibodies in healthy people, while other C-CS B cells are naturally autoreactive. We interpret these findings to indicate that autoreactive B cells can either be induced to class switch to IgD or autoreactive B cell clones that use IgD as the B cell receptor are not effectively deleted. Determining the mechanism by which the majority of C-CS B cells are autoreactive may be important in understanding peripheral tolerance mechanisms and may provide insight to the enigmatic function of the secreted IgD antibody.
