RAG1 and RAG2 expression by B cell subsets from human tonsil and peripheral blood.
It has been suggested that B cells acquire the capacity for secondary V(D)J recombination during germinal center (GC) reactions. The nature of these B cells remains controversial. Subsets of tonsil and blood B cells and also individual B cells were examined for the expression of recombination-activating gene (RAG) mRNA. Semiquantitative analysis indicated that RAG1 mRNA was present in all tonsil B cell subsets, with the largest amount found in naive B cells. RAG2 mRNA was only found in tonsil naive B cells, centrocytes, and to a lesser extent in centroblasts. Neither RAG1 nor RAG2 mRNA was routinely found in normal peripheral blood B cells. In individual tonsil B cells, RAG1 and RAG2 mRNAs were found in 18% of naive B cells, 22% of GC founder cells, 0% of centroblasts, 13% of centrocytes, and 9% of memory B cells. Individual naive tonsil B cells containing both RAG1 and RAG2 mRNA were activated (CD69(+)). In normal peripheral blood approximately 5% of B cells expressed both RAG1 and RAG2. These cells were uniformly postswitch memory B cells as documented by the coexpression of IgG mRNA. These results indicate that coordinate RAG expression is not found in normal peripheral naive B cells but is up-regulated in naive B cells which are activated in the tonsil. With the exception of centroblasts, RAG1 and RAG2 expression can be found in all components of the GC, including postswitch memory B cells, some of which may circulate in the blood of normal subjects.
Girschick
H J
HJ
Department of Internal Medicine, Harold C. Simmons Arthritis Research Center, University of Texas Southwestern Medical Center, Dallas, TX 75235, USA.
Grammer
A C
AC
Nanki
T
T
Mayo
M
M
Lipsky
P E
PE
D000328:Adult; D016175:B-Lymphocyte Subsets / Q000201:enzymology* / Q000276:immunology / Q000378:metabolism; D002648:Child; D004253:DNA Nucleotidylexotransferase / Q000096:biosynthesis / Q000235:genetics; D004254:DNA Nucleotidyltransferases / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000097:blood / Q000235:genetics*; D043382:DNA-Formamidopyrimidine Glycosylase; D005786:Gene Expression Regulation / Q000276:immunology; D016654:Genes, RAG-1 / Q000276:immunology*; D018398:Homeodomain Proteins / Q000096:biosynthesis / Q000097:blood / Q000235:genetics*; D006801:Humans; D007072:Immunoglobulin D / Q000096:biosynthesis / Q000235:genetics; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000235:genetics; D007147:Immunoglobulin Light Chains; D054444:Immunoglobulin Light Chains, Surrogate; D007135:Immunoglobulin Variable Region / Q000096:biosynthesis / Q000235:genetics; D007146:Immunoglobulin lambda-Chains / Q000096:biosynthesis / Q000235:genetics; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics; D009699:N-Glycosyl Hydrolases / Q000096:biosynthesis / Q000235:genetics; D009687:Nuclear Proteins; D014066:Palatine Tonsil / Q000201:enzymology* / Q000276:immunology / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D013234:Stem Cells / Q000276:immunology / Q000378:metabolism; D019895:Transposases / Q000235:genetics*; D045567:VDJ Recombinases
D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D007072:Immunoglobulin D; D007074:Immunoglobulin G; D007147:Immunoglobulin Light Chains; D054444:Immunoglobulin Light Chains, Surrogate; D007135:Immunoglobulin Variable Region; D007146:Immunoglobulin lambda-Chains; D008562:Membrane Glycoproteins; D009687:Nuclear Proteins; C499311:RAG2 protein, human; D012333:RNA, Messenger; C064655:V(D)J recombination activating protein 2; C064658:RAG-1 protein; D004254:DNA Nucleotidyltransferases; D019895:Transposases; D045567:VDJ Recombinases; D004253:DNA Nucleotidylexotransferase; D009699:N-Glycosyl Hydrolases; D043382:DNA-Formamidopyrimidine Glycosylase