Immunoglobulin kappa light chain gene rearrangement is impaired in mice deficient for DNA polymerase mu.
Bertocci B, De Smet A, Berek C, Weill JC, Reynaud CA.
Institut National Français de Recherche Médicale U373, Faculté de Médecine Necker-Enfants Malades, 156 rue de Vaugirard, 75730 Paris 15, France.
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.
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PMID: 12932354 [PubMed - indexed for MEDLINE]