title: Expression of the recombination-activating genes in extrafollicular lymphocytes but no apparent reinduction in germinal center reactions in human tonsils.
abstract: V(D)J recombination in lymphocytes is mediated by 2 recombination-activating genes, RAG1 and RAG2, which are expressed during lymphocyte development in bone marrow and thymus. Prompted by studies reporting re-expression of the RAGs in germinal center B cells, the expression of RAGs and terminal deoxynucleotidyl transferase (TdT) in human lymphoid tissues was examined using in situ hybridization and immunohistochemistry, respectively. Here it is shown that RAGs and TdT are not reinduced in germinal center reactions. However, RAG(+)/TdT(+) cells are frequently present in extrafollicular areas of tonsils mainly at the boundary between lymphoid tissue and fibrous scaffold. Phenotypic analyses suggest that these cells are B cells. Finally, it is shown that RAG(+)/TdT(+) cells are found more frequently in tonsils than in other peripheral lymphoid tissues. This may reflect an increased influx of RAG(+)/TdT(+) cells as a result of higher antigenic stimulation at this site. Alternatively, this observation may indicate that the tonsils are an additional site of lymphocyte ontogeny.
authors.affiliation: Pathologisches Institut, Friedrich-Alexander-Universität, Erlangen, Germany.
authors.forename: Nadine
authors.initials: N
authors.lastname: Meru
authors.forename: Andreas
authors.initials: A
authors.lastname: Jung
authors.forename: Irith
authors.initials: I
authors.lastname: Baumann
authors.forename: Gerald
authors.initials: G
authors.lastname: Niedobitek
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001327:Autoimmune Diseases / Q000276:immunology / Q000473:pathology; D001402:B-Lymphocytes / Q000378:metabolism; D001853:Bone Marrow / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D004253:DNA Nucleotidylexotransferase / Q000096:biosynthesis / Q000235:genetics; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D004790:Enzyme Induction; D005260:Female; D005786:Gene Expression Regulation; D018858:Germinal Center / Q000166:cytology* / Q000276:immunology; D018398:Homeodomain Proteins / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D006965:Hyperplasia; D007082:Ileum / Q000166:cytology / Q000276:immunology; D007124:Immunoenzyme Techniques; D017403:In Situ Hybridization; D007223:Infant; D008180:Lupus Erythematosus, Systemic / Q000276:immunology / Q000473:pathology; D016131:Lymphocyte Subsets / Q000378:metabolism*; D008221:Lymphoid Tissue / Q000276:immunology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins; D009928:Organ Specificity; D014066:Palatine Tonsil / Q000276:immunology* / Q000473:pathology / Q000648:ultrastructure; D013950:Thymus Gland / Q000473:pathology
chemical_list: D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D009687:Nuclear Proteins; C499311:RAG2 protein, human; C064655:V(D)J recombination activating protein 2; C064658:RAG-1 protein; D004253:DNA Nucleotidylexotransferase