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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.
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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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