The Journal of Experimental Medicine
VeriKine-HS Human IFN-Beta
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Published 2 February 2004. doi:10.1084/jem.20031712
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 199, Number 3, 337-346
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Editing Anti-DNA B Cells by V{lambda}x

Yijin Li1, Yoram Louzoun2, and Martin Weigert1

1 Department of Molecular Biology, Princeton University, Princeton, NJ 08544
2 Department of Mathematics, Bar Ilan University, Ramat Gan 52900, Israel

Address correspondence to Yijin Li, Gwen Knapp Center for Lupus and Immunology Research, The University of Chicago, 924 East 57th St., Rm. 413A, Chicago, IL 60637. Phone: (773) 702-2719; Fax: (773) 702-1576; email: yijinli{at}uchicago.edu

Receptor editing is performed by replacement of V{kappa} genes that contribute to autoreactivity. In addition, the C{kappa} locus can be deleted by V{kappa} rearrangement to intronic or 3' of C{kappa} RS sequences (also referred to as {kappa} deletion elements). B cells that delete the C{kappa} can then express {lambda} light chains. However, the {lambda} locus, either of man or mouse, does not allow V gene replacement. Nor does it appear to be deleted. Therefore, editing of autoreactive {lambda} B cells may require alternative pathways. We have found that in anti-DNA heavy chain transgenic mice (tgs) VH3H9/56R, B cells that express anti-DNA receptors comprised of {lambda}1 in association with an anti-DNA heavy chain often coexpress a {kappa} chain that prevents DNA binding. We speculate that such isotypically included cells may have low anti-DNA receptor densities, a feature that may lead to self-tolerance. Here we describe a mechanism of preventing DNA binding by expression of a rarely used member of the V{lambda} family, V{lambda}x. The {lambda}x B cells of the tgs also express CD25 and may represent B cells that have exhausted light chain editing possibilities.

Key Words: autoimmunity • lupus • CD25 • light chain • myelin basic protein

Abbreviations used in this paper: IEP, isoelectric point; MBP, myelin basic protein; tg, transgenic mouse; tgs, transgenic mice.


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