Expression and function of recombination activating genes in mature B cells

Abstract

Recombination activating genes, RAG-1 and RAG-2, encode proteins that catalyze the rearrangement of immunoglobulin genes in B cells and T cell receptor genes in T cells to generate the diversity of these important recognition molecules in immune system. It has been believed that these gene rearrangements occur exclusively in premature stages of B and T lymphocytes, consistent with the observation that RAG expression is downregulated in mature lymphocytes. However, recent studies have revealed that even mature B cells in peripheral lymphoid tissues can reexpress RAG-1 and RAG-2 proteins following immunization. Strikingly, RAG-expressing B cells are localized in the germinal centers (GCs) of secondary lymphoid tissues in which somatic hypermutations, isotype switching, and affinity maturation of antibodies take place. Recently, it has been shown that RAG proteins thus induced are functional and can mediate the secondary rearrangement of Ig genes (receptor editing) at mature stages of B cells. Evidence is accumulating suggesting that GCs are regarded as a primary lymphoid tissue. In the present review, we briefly summarize recent advances in the expression and the characterization of RAG proteins and discuss their possible role in mature B cells in relation to the diversification and the selection of B cell repertoire in GCs.