IMMATURE SURFACE IG-CELLS CAN CONTINUE TO REARRANGE KAPPA-L-CHAIN ANDLAMBDA-L-CHAIN GENE LOCI( B)

Pro and pre B cells possess the long-term capacity to proliferate in v itro on stromal cells and interleukin 7 (IL-7) and can differentiate t o surface immunoglobulin (sIg+) cells upon removal of IL-7 from the cu ltures. A key event in this differentiation is the extensive cell loss due to apoptosis. Because the proto-oncogene bcl-2 can promote cell s urvival, we established pre-B cell lines from Emu-bcl-2 transgenic mic e. These pre-B cells have the same properties as those derived from no n-bcl-2 transgenic mice except that they do not die by apoptosis. This allowed us to study the fate of newly formed B cells in vitro for a l onger period of time. Here we show that early during the differentiati on of pre-B cells, upregulation of RAG-1 and RAG-2 expression go hand in hand with rearrangements of the Ig gene loci. Moreover, the newly f ormed sIg+ B cells continue to express RAG-1 and RAG-2 and continue to rearrange L chain gene loci, even in the absence of proliferation, in an orderly fashion, so that kappaL+ sIg+ cells can become lambdaL+ sI g+ or sIg- cells, whereas lambdaL+ sIg+ cells can become sIg-, but not kappaL+ sIg+ cells. Thus, deposition of a complete Ig molecule on the surface of a B cell does not automatically stop the Ig-rearrangement machinery.