Expression of RAGs in peripheral B cells outside germinal centers is associated with the expression of CD5.
Previous studies have indicated that mature B cells reactivate secondary V(D)J recombination inside and outside the germinal center (GC) of peripheral lymphoid organs. The nature of the B cells undergoing Ig rearrangement before they enter GC is unknown. In this study, we present evidence that activated mature CD5-positive human tonsil B cells coexpress both RAG1 and RAG2 mRNA and protein, and display DNA cleavage resulting from their recombinase activity. Furthermore, in vitro activation of CD5-negative naive mature B cells by IgR and CD40 cross-linking induces expression of CD5 on a subset of cells, and leads to the up-regulation of RAG1 and RAG2 only in cells turned positive for CD5. Thus, RAG gene expression is closely related to CD5 expression outside GCs. These data suggest that CD5 is associated with receptor revision in activated mature B cells and likely to promote expression of suitable IgR capable of initiating the GC reaction.
Hillion
Sophie
S
Laboratory of Immunology, Brest University Medical School Hospital, Brest, France.
Saraux
Alain
A
Youinou
Pierre
P
Jamin
Christophe
C
D000293:Adolescent; D016175:B-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D018956:CD5 Antigens / Q000096:biosynthesis* / Q000502:physiology; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D005434:Flow Cytometry; D015322:Gene Rearrangement, B-Lymphocyte; D016654:Genes, RAG-1; D018858:Germinal Center / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D018398:Homeodomain Proteins / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D007072:Immunoglobulin D / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000235:genetics; D009687:Nuclear Proteins; D014066:Palatine Tonsil / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D011947:Receptors, Antigen, B-Cell / Q000096:biosynthesis / Q000235:genetics; D014158:Transcription, Genetic / Q000276:immunology; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology
D018956:CD5 Antigens; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D007072:Immunoglobulin D; D009687:Nuclear Proteins; C499311:RAG2 protein, human; D011947:Receptors, Antigen, B-Cell; C064655:V(D)J recombination activating protein 2; C064658:RAG-1 protein