Induction of sterile transcription from the kL chain gene locus in V(D)J recombinasedeficient progenitor B cells
B cell development In RAG-2-deficient (RAG-2T) mice is Impeded at an early stage, due to the Inability of these animals to rearrange their endogenous Ig gene loci. Expression of an Eft-bcl-2 transgene in these mice did not change this phenotype. However, stromal cell/IL-7-reactive B cell progenitors (pro-B cells) were found In fetal liver and bone marrow of RAG-2T and RAG-2VEfirbcl-2 transgenlc mice In numbers comparable to normal mice. Like cells from normal mice they are cklt + , surrogate L
... lt + , surrogate L chain + and CD25~, and can proliferate In vitro for long periods of time. Upon IL-7 deprivation, they can be Induced to differentiate into c-klt~, surrogate L chain'and CD25 + cells that are no longer clonable on stromal cells and IL-7. Furthermore, sterile transcription from the KL chaln gene loci is induced. The latter was also observed with pro-B cells directly Isolated ex vivo from the bone marrow of RAG-2-deflclent animals. The results suggest that progenitor B cell differentiation can occur In cells from V(D)J recombinase-deficient mice to the stage where tcL chain gene rearrangements would normally be initiated. It further indicates that some molecular programs of early B cell differentiation can take place In the absence of Ig gene rearrangements.