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Autoreactivity and allelic inclusion in a B cell nuclear transfer mouse

Nature Immunology volume 5, pages 1282–1287 (2004)Cite this article

Abstract

Lymphocytes typically express only one functional antigen receptor, a restriction contributed to by allelic exclusion. Here we have analyzed B lymphocyte development in offspring of a mouse generated by nuclear transfer using a single donor B lymphocyte. In this mouse, all immunoglobulin alleles were inherited as found in the donor lymphocyte. This donor cell had two rearranged immunoglobulin light chain alleles, both directing the synthesis of light chains that could form functional antigen receptors, one of which was autoreactive. Progeny mice carrying this immunoglobulin light chain allele produced mature B cells, some of which continued to express the autoreactive receptor but required another rearrangement to rescue them from negative selection. Such receptor editing failed to destroy expression of one original light chain allele, thereby recreating dual receptor expression on these surviving B cells. We suggest that autoreactive antibodies in serum of mice and humans are due in part to such 'passenger' receptors.

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Figure 1: The immunoglobulin alleles of the B cell nuclear transfer mouse.
Figure 2: Autoreactivity of the Hxkb4 receptor.
Figure 3: Deletion of B cells with the kb4 receptor.
Figure 4: Editing and allelic inclusion of the kb4 receptor.

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Acknowledgements

We thank F. Nasseri, M. Weigert, D. Nemazee, and E. Weiss for discussions; K. Hochedlinger and R. Jaenisch for providing nuclear transfer mice; and M. Schlissel for the human Cκ mouse generated by M. Nussenzweig. Supported by a National Institutes of Health (R01 AI41570) and a University of California Biostar Discovery Grant.

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  1. Department of Microbiology and Immunology, University of California, San Francisco, 94143-0414, California, USA

    Tobias Gerdes & Matthias Wabl

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Correspondence to Matthias Wabl.

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Supplementary information

Supplementary Fig. 1

Sequence of κ light chain alleles. (PDF 231 kb)

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Gerdes, T., Wabl, M. Autoreactivity and allelic inclusion in a B cell nuclear transfer mouse. Nat Immunol 5, 1282–1287 (2004). https://doi.org/10.1038/ni1133

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