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-activa ting gene (RAG) mRNA, Semiquantitative analysis indicated that RAGI mRNA wa s present in all tonsil B cell subsets, with the largest amount found in na ive 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 rou tinely found in normal peripheral blood B cells. In individual tonsil B cel ls, RAG1 and RAG2 mRNAs were found in 18% of naive B cells, 22% of GC found er 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 ac tivated (CD69(+)). In normal peripheral blood similar to5% of B cells expre ssed both RAG1 and RAG2. These cells were uniformly postswitch memory B cel ls as documented by the coexpression of IgG mRNA. These results indicate th at coordinate RAG expression is not found in normal peripheral naive B cell s but is up-regulated in naive B cells which are activated in the tonsil. W ith the exception of centroblasts, RAG1 and RAG2 expression can be found in all components of the GC, including postswitch memory B cells, some of whi ch may circulate in the blood of normal subjects.