DUAL ROLE OF RAG2 IN V(D)J RECOMBINATION - CATALYSIS AND REGULATION OF ORDERED IG GENE ASSEMBLY

Immunoglobulin genes are assembled during lymphoid development by a se ries of site-specific rearrangements that are tightly regulated to ens ure that functional antibodies are generated in B (but not T) cells an d that a unique receptor is present on each cell. Because a common V(D )J recombinase comprising RAG1 and RAG2 proteins is used for both B- a nd T-cell antigen receptor assembly, lineage-specific rearrangement mu st be modulated through differential access to sites of recombination, We show here that the C-terminus of the RAG2 protein, although dispen sable for the basic recombination reaction and for Ig heavy chain Du t o JH joining, is essential for efficient V-H to DJ(H) rearrangement at the IgH locus, Thus, the RAG2 protein plays a dual role in V(D)J reco mbination, acting both in catalysis of the reaction and in governing a ccess to particular loci.