title: Within germinal centers, isotype switching of immunoglobulin genes occurs after the onset of somatic mutation.
abstract: Human tonsillar B cells were separated into naive IgD+CD38-CD23- (Bm1) and IgD+CD38-CD23 (Bm2), germinal center IgD-CD38+CD23- centroblasts (Bm3) and IgD-CD38+CD77- centrocytes (Bm4) and memory IgD-CD38- (Bm5) subsets. Previous IgVH sequence analysis concluded that the triggering of somatic mutations occurs during the transition from Bm2 subset into the Bm3 subset. To determine the initiation of isotype switching, sterile transcript expression was analyzed by amplification, cloning, and sequencing. A selective sterile I gamma, I alpha, and I epsilon expression was observed at centrocyte (Bm4) stage, suggesting that isotype switch is triggered within germinal centers, after somatic mutation is initiated with centroblasts (Bm3). Finally, the high level of 5'S gamma-S mu 3' DNA switching circles observed in germinal center B cells indicates that within human tonsils, germinal center is a major location for isotype switching.
authors.affiliation: Schering-Plough Laboratory for Immunological Research, Dardilly, France.
authors.forename: Y J
authors.initials: YJ
authors.lastname: Liu
authors.forename: F
authors.initials: F
authors.lastname: Malisan
authors.forename: O
authors.initials: O
authors.lastname: de Bouteiller
authors.forename: C
authors.initials: C
authors.lastname: Guret
authors.forename: S
authors.initials: S
authors.lastname: Lebecque
authors.forename: J
authors.initials: J
authors.lastname: Banchereau
authors.forename: F C
authors.initials: FC
authors.lastname: Mills
authors.forename: E E
authors.initials: EE
authors.lastname: Max
authors.forename: H
authors.initials: H
authors.lastname: Martinez-Valdez
mesh_terms: D001402:B-Lymphocytes / Q000276:immunology; D001483:Base Sequence; D002460:Cell Line; D004247:DNA / Q000032:analysis; D004249:DNA Damage / Q000276:immunology; D015322:Gene Rearrangement, B-Lymphocyte / Q000276:immunology*; D005803:Genes, Immunoglobulin; D018858:Germinal Center / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D000949:Histocompatibility Antigens Class II / Q000235:genetics*; D006801:Humans; D017578:Immunoglobulin Class Switching / Q000276:immunology*; D008969:Molecular Sequence Data; D009154:Mutation / Q000276:immunology*; D014066:Palatine Tonsil / Q000276:immunology; D017384:Sequence Deletion / Q000276:immunology; D014158:Transcription, Genetic / Q000276:immunology
chemical_list: D000949:Histocompatibility Antigens Class II; D004247:DNA