Autoreactivity and allelic inclusion in a B cell nuclear transfer mouse.
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.
Gerdes
Tobias
T
Department of Microbiology and Immunology, University of California, San Francisco, California 94143-0414, USA.
Wabl
Matthias
M
D000483:Alleles; D000818:Animals; D015551:Autoimmunity / Q000235:genetics / Q000276:immunology*; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D002467:Cell Nucleus / Q000235:genetics / Q000276:immunology; D002470:Cell Survival; D017353:Gene Deletion; D015322:Gene Rearrangement, B-Lymphocyte / Q000235:genetics*; D005803:Genes, Immunoglobulin / Q000235:genetics*; D007143:Immunoglobulin Heavy Chains / Q000235:genetics / Q000276:immunology; D007147:Immunoglobulin Light Chains / Q000235:genetics / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D053652:Nuclear Transfer Techniques
D007143:Immunoglobulin Heavy Chains; D007147:Immunoglobulin Light Chains