title: V(D)J recombinase activity in a subset of germinal center B lymphocytes.
abstract: Reexpression of the V(D)J recombinase-activating genes RAG1 and RAG2 in germinal center B cells creates the potential for immunoglobulin gene rearrangement and the generation of new antigen receptor specificities. Intermediate products of V(D)J recombination are abundant in a subset of germinal center B cells, demonstrating that the kappa immunoglobulin light-chain locus becomes a substrate for renewed V(D)J recombinase activity. This recombinationally active cell compartment contains many heavy-chain VDJ rearrangements that encode low-affinity or nonfunctional antibody. In germinal centers, secondary V(D)J recombination may be induced by diminished binding to antigen ligands, thereby limiting abrupt changes in receptor specificity to B cells that are usually eliminated from the germinal center reaction. This restriction preserves efficient antigen-driven selection in germinal centers while allowing for saltations in the somatic evolution of B cells.
authors.affiliation: Department of Microbiology and Immunology and Program in Molecular and Cell Biology, University of Maryland School of Medicine, 655 West Baltimore Street, Baltimore, MD 21201, USA.
authors.forename: S
authors.initials: S
authors.lastname: Han
authors.forename: S R
authors.initials: SR
authors.lastname: Dillon
authors.forename: B
authors.initials: B
authors.lastname: Zheng
authors.forename: M
authors.initials: M
authors.lastname: Shimoda
authors.forename: M S
authors.initials: MS
authors.lastname: Schlissel
authors.forename: G
authors.initials: G
authors.lastname: Kelsoe
mesh_terms: D000818:Animals; D000916:Antibody Diversity; D001402:B-Lymphocytes / Q000201:enzymology* / Q000276:immunology; D004254:DNA Nucleotidyltransferases / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics; D015322:Gene Rearrangement, B-Lymphocyte; D005803:Genes, Immunoglobulin; D016654:Genes, RAG-1; D018858:Germinal Center / Q000166:cytology / Q000276:immunology*; D007114:Immunization; D007133:Immunoglobulin Joining Region / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000235:genetics; D007145:Immunoglobulin kappa-Chains / Q000235:genetics; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D011995:Recombination, Genetic; D045567:VDJ Recombinases
chemical_list: D004268:DNA-Binding Proteins; D007133:Immunoglobulin Joining Region; D007135:Immunoglobulin Variable Region; D007145:Immunoglobulin kappa-Chains; C499308:Rag2 protein, mouse; C064655:V(D)J recombination activating protein 2; D004254:DNA Nucleotidyltransferases; D045567:VDJ Recombinases