Immunoglobulin kappa light chain gene rearrangement is impaired in mice deficient for DNA polymerase mu.
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.
Bertocci
Barbara
B
Institut National Français de Recherche Médicale U373, Faculté de Médecine Necker-Enfants Malades, 156 rue de Vaugirard, 75730 Paris 15, France.
De Smet
Annie
A
Berek
Claudia
C
Weill
Jean-Claude
JC
Reynaud
Claude-Agnès
CA
D000818:Animals; D001402:B-Lymphocytes / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D001483:Base Sequence; D022801:Complementarity Determining Regions; D018076:DNA, Complementary / Q000235:genetics; D004259:DNA-Directed DNA Polymerase / Q000172:deficiency* / Q000235:genetics; D015328:Gene Rearrangement, B-Lymphocyte, Light Chain; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010641:Phenotype; D013045:Species Specificity; D014018:Tissue Distribution
D022801:Complementarity Determining Regions; D018076:DNA, Complementary; C407743:DNA polymerase mu; D004259:DNA-Directed DNA Polymerase