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Allelic and Isotypic Light Chain Inclusion in Peripheral B Cells from Anti-DNA Antibody Transgenic C57BL/6 and BALB/c Mice¹

Esther J. Witsch^2,* and Eldad Bettelheim

^* Department of Pathology, Gwen Knapp Center for Lupus and Immunology Research, University of Chicago, Chicago, IL 60637; and Department of Physical Sciences, James Franck Institute, University of Chicago, Chicago, IL 60637

Most mature B lymphocytes express one BCR L chain, or , but recent work has shown that there are exceptions in that some B lymphocytes express both and and some even bear two different L chains. Using the anti-DNA H chain-transgenic mouse, 56R, we find that B cells with pre-existing autoreactivity are especially subject to L chain inclusion. Specifically, we show that isotypic and allelic inclusion enables autoreactive B cells to bypass central tolerance giving rise to B cells that retain dangerous features. One receptor in dual receptor B cells is an editor L chain, i.e., neutralizes or alters self-reactivity of the 56R H chain transgene. We compare the 56R mouse when on the C57/BL/6 background, a strain prone to autoimmunity, with that of 56R when on the BALB/c background, a strain that resists autoimmunity. In the B6.56R mouse, polyreactive B cells with dual L chain move to the follicular B cell compartment. Their localization in the follicular compartment may explain the ease with which B cells in the B6.56R differentiate into autoantibody-producing plasma cells. Likewise, in the BALB/c.56R mouse, dual L chain B cells are found in the follicular B cell compartment. Yet, the lack of autoantibody-producing plasma cells in the BALB/c.56R suggests that postfollicular tolerance checkpoints are intact. The J usage in dual L chain B cells suggests increased receptor editing activity and is consistent with the expected distribution of J genes in our computational model for random selection of J.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by National Institutes of Health Grant GM02964-32, by a grant from the Lupus Research Institute, and by the Israeli Science Foundation.

² Address correspondence and reprint requests to Dr. Esther J. Witsch at the current address: Department of Biological Regulation, Weizmann Institute of Science, Candiotty Building, POB 26, Rehovot 76100, Israel. E-mail address: esther.witsch{at}weizmann.ac.il

³ Abbreviations used in this paper: MZ, marginal zone; cGvH, chronic graft-vs-host reaction; FR, framework region.

⁴ The online version of this article contains supplemental material.

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