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The Journal of Immunology, 2001, 166: 377-386.
Copyright © 2001 by The American Association of Immunologists

RAG1 and RAG2 Expression by B Cell Subsets from Human Tonsil and Peripheral Blood1

Hermann J. Girschick, Amrie C. Grammer2, Toshihiro Nanki2, Marlyn Mayo and Peter E. Lipsky2,3

Department of Internal Medicine, Harold C. Simmons Arthritis Research Center, University of Texas Southwestern Medical Center, Dallas, TX 75235

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 ~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.




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