V(D)J RECOMBINASE ACTIVITY IN A SUBSET OF GERMINAL CENTER B-LYMPHOCYTES

Reexpression of the V(D)J recombinase-activating genes RAG1 and RAG2 i n germinal center B cells creates the potential for immunoglobulin gen e rearrangement and the generation of new antigen receptor specificiti es. intermediate products of V(D)J recombination are abundant in a sub set of germinal center B cells, demonstrating that the kappa immunoglo bulin light-chain locus becomes a substrate for renewed V(D)J recombin ase activity. This recombinationally active cell compartment contains many heavy-chain VDJ rearrangements that encode low-affinity or nonfun ctional antibody. In germinal centers, secondary V(D)J recombination m ay be induced by diminished binding to antigen ligands, thereby limiti ng abrupt changes in receptor specificity to B cells that are usually eliminated from the germinal center reaction, This restriction preserv es efficient antigen-driven selection in germinal centers while allowi ng for saltations in the somatic evolution of B cells.