Immunoglobulin gene expression only in the right cells at the right time

Study of immunoglobulin gene transcriptional control has disclosed a complexity that rivals that of the antibody repertoire itself. Although some DNA sequences that regulate transcription of these genes were identified almost a decade ago, additional regulatory sequences continue to be discovered, some in regions far removed (as much as 200 kb) from the actual site of transcription. This has invoked models of regulation in which the higher-order structure of chromatin must be taken into account. Within the regulatory DNA sequences themselves, there is a bewildering array of sites that bind proteins and a growing catalog of proteins that can bind each of those sites. The proteins are believed to be the physical link between the regulatory DNA sequences and the protein machinery actually carrying out transcription. Specific interactions among proteins that can bind the same site and among proteins that bind different sites have been described. A challenge remaining is to identify those interactions that occur in vivo and that lead to progressively more efficient Ig production in the developing B cell, but which disallow Ig production in non-B cells.