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Immunity. 2003 Aug;19(2):203-11.

Immunoglobulin kappa light chain gene rearrangement is impaired in mice deficient for DNA polymerase mu.

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1
Institut National Français de Recherche Médicale U373, Faculté de Médecine Necker-Enfants Malades, 156 rue de Vaugirard, 75730 Paris 15, France.

Abstract

DNA polymerase mu (pol mu) is a template-dependent polymerase closely related to the lymphoid-specific enzyme terminal deoxynucleotidyl transferase (TdT). We report here the phenotype of pol mu-deficient mice. Such animals display an abnormal B cell differentiation, with a specific alteration in the IgM- to IgM+ transition in bone marrow. In all mice, Ig light chain gene rearrangement is impaired at the level of the Vkappa-Jkappa and Vlambda-Jlambda junctions, which show extensive nibbling of both coding extremities. These alterations lead to a profound defect in the peripheral B cell compartment which, although variable between animals, results in an average 40% reduction in the splenic B cell fraction. Pol mu appears, therefore, as a key element contributing to the relative homogeneity in size of light chain CDR3 and taking part in Ig gene rearrangement at a stage where TdT is no longer expressed.

PMID:
12932354
[Indexed for MEDLINE]
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