Control of Expression of Immunoglobulin Genes

Abstract

Immunoglobulin genes become activated during the development of B lymphocytes by sequential rearrangement of heavy and light chain genes (Alt et al., 1986). The rearrangement of immunoglobulin genes requires that the VDJ recombinase is present and that the target Ig genes are accessible for recombination (Alt et al., 1987). These events appear to be tightly controlled in a way which leads to allelic and isotypic exclusion of Ig genes (reviewed by Engler and Storb, 1988). Some years ago we began to use transgenic mice to study the mechanisms of allelic and isotypic exclusion (Brinster et al., 1983). This work, as well as the results from many other laboratories, has led to the following conclusions (reviewed by Storb, 1988): There are two levels of control of Ig gene rearrangement; at the early preB cell stage when a correct rearrangement of a heavy chain gene has been made, the further rearrangement of H genes is stopped, perhaps at the level of VD joining, while the VDJ specific recombinase continues to exist and now rearranges κ and/or λ genes. The final stop of the rearrangement mechanism apparently occurs by a shutoff of the recombinase signaled by the assembly of a complete membrane bound Ig molecule, consisting of a μ. chain and a κ or λ light chain.