The Journal of Experimental Medicine
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Published online December 15, 2008
doi:10.1084/jem.20082053
The Journal of Experimental Medicine, Vol. 205, No. 13, 2985-2994
The Rockefeller University Press, 0022-1007 $30.00
© 2008 Panigrahi et al.
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ARTICLE

 RS rearrangement frequency as a marker of receptor editing in lupus and type 1 diabetes

Anil K. Panigrahi1, Noah G. Goodman1, Robert A. Eisenberg2, Michael R. Rickels3, Ali Naji4, and Eline T. Luning Prak1

1 Department of Pathology and Laboratory Medicine, 2 Division of Rheumatology, 3 Division of Endocrinology, Diabetes and Metabolism, and 4 Harrison Department of Surgical Research, University of Pennsylvania School of Medicine, Philadelphia, PA 19104

CORRESPONDENCE Eline T. Luning Prak: luning{at}mail.med.upenn.edu

Continued antibody gene rearrangement, termed receptor editing, is an important mechanism of central B cell tolerance that may be defective in some autoimmune individuals. We describe a quantitative assay for recombining sequence (RS) rearrangement that we use to estimate levels of antibody light chain receptor editing in various B cell populations. RS rearrangement is a recombination of a noncoding gene segment in the {kappa} antibody light chain locus. RS rearrangement levels are highest in the most highly edited B cells, and are inappropriately low in autoimmune mouse models of systemic lupus erythematosus (SLE) and type 1 diabetes (T1D), including those without overt disease. Low RS rearrangement levels are also observed in human subjects with SLE or T1D.

Abbreviations used: BP-1, BP-1 (aminopeptidase A); Fr., fraction; iRS, intron RS; KDE, {kappa} deleting element; NOD, nonobese diabetic; NOR, nonobese resistant; PTPN22, protein tyrosine phosphatase nonreceptor 22; RS, recombining sequence; SLE, systemic lupus erythematosis; T1D, type 1 diabetes.

© 2008 Panigrahi et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jem.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).


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