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Proc Natl Acad Sci U S A. 2006 May 16;103(20):7747-52. Epub 2006 May 8.

Light chain inclusion permits terminal B cell differentiation and does not necessarily result in autoreactivity.

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  • 1Laboratoire d'Immunologie, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 6101, Equipe Labellisée la Ligue, Université de Limoges, F-87025 Limoges, France.

Abstract

Mice in which the Jkappa cluster was replaced with a VkappaJkappa rearranged gene were studied. More than 90% of B cells from homozygous mutant mice expressed the transgenic kappa chain but showed a slightly reduced level of kappa transcripts compared with WT B lymphocytes. Light chain inclusion was apparent in 10% of B cells from these mice and raised 25% in hemizygous mice with a still lower expression of the knockin kappa chain. Beyond the rules of clonal selection, peripheral B cells developed in such animals, with included cells being activated and differentiating into class-switched or antibody-secreting cells. The high amount of included mature B cells was associated with an increase of hybrid kappa/lambda immunoglobulins but not with the increased prevalence of autoantibodies. Altogether, these data suggest that light chain exclusion prevalent in normal B cells mostly results from ordered rearrangements and stochastic mechanisms but is neither tightly ensured by a stringent cell selection process nor absolutely required for normal B cell function.

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