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The Journal of Immunology, 2009, 182, 6143 -6148
Copyright © 2009 by The American Association of Immunologists, Inc.
doi:10.4049/jimmunol.0803610

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*Lupus

Autoreactive Anti-DNA Transgenic B Cells in Lupus-Prone New Zealand Black/New Zealand White Mice Show Near Perfect L Chain Allelic Exclusion1

Efi Makdasi, Ruth Fischel, Inbal Kat and Dan Eilat

Department of Medicine, Hadassah University Hospital, Faculty of Medicine, Hebrew University, Jerusalem, Israel

Recent work on B cell tolerance and autoimmunity has suggested the L chain allelic inclusion is a property of autoreactive B cells and is closely linked to receptor editing. Allelic inclusion could rescue autoreactive B cells from clonal deletion by reducing their effective BCR surface density. We have investigated this phenomenon in anti-DNA producing hybridomas, derived from different strains of Ig gene-targeted, lupus-prone NZB/NZW mice. Our results indicate that isotype and allelic exclusion was strictly maintained in most high- and low-affinity, edited and nonedited, anti-DNA transgenic B cells. However, a substantial fraction of the anti-DNA hybridomas expressed a very restricted set of nonproductively rearranged L chain mRNA, in addition to the productive anti-DNA L chain. The aberrant L chains could have a role in the selection and survival of autoreactive B cells in these autoimmune mice.

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 the Israel Science Foundation, Founded by the Academy of Science and Humanities. E. M. was supported by a fellowship from the ISEF Foundation.

2 Address correspondence and reprint requests to Dr. Dan Eilat, Department of Medicine, Hadassah University Hospital, Ein Kerem, Jerusalem 91120, Israel. E-mail address: eilatd{at}cc.huji.ac.il

3 Abbreviations used in this paper: Tg, transgenic; PTC, premature termination codon.

4 The online version of this article contains supplemental material.







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