Immunoglobulin V/J recombination is accompanied by deletion of joining site variable region segments

A site-specific recombination event is responsible for the somatic activation of immunoglobulin genes and for generating a major share of immunoglobulin gene diversity. Although several possible mechanisms can be proposed to account for this process, recombination accompanied by deletion is a particularly attractive mechanism because it might utilize inverted repeat sequences noted on the 3' side of all variable regions and on the 5' side of all joining site segments, thus far studied. Testing this model is complicated by the fact that antibody cells are at least diploid and gene segments on the inactive chromosome can obscure deletions occurring within the active gene. Accordingly, we have screened several immunoglobulin-producing plasmacytoma lines to select those in which both chromosomes are rearranged. By using appropriate cell lines and variable and joining region probes in in situ hybridization experiments, we show that recombination is accompanied by the deletion of both variable and joining region genes. These experiments also allow us to map the site of V/J recombination of several active immunoglobulin genes and suggest an order and orientation for variable, joining, and constant region sequences.