Induction of sterile transcription from the kappa L chain gene locus in V(D)J recombinase-deficient 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 E mu-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 live and bone marrow of RAG-2T and RAG-2T/E mu-bcl-2 transgenic mice in numbers comparable to normal mice. Like cells from normal mice they are c-kit+, 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-kit-, surrogate L chain- and CD25+ cells that are no longer clonable on stromal cells and IL-7. Furthermore, sterile transcription from the kappa L chain gene loci is induced. The latter was also observed with pro-B cells directly isolated ex vivo from the bone marrow of RAG-2-deficient animals. The results suggest that progenitor B cell differentiation can occur in cells from V(D)J recombinase-deficient mice to the stage where kL 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.
Grawunder
U
U
Basel Institute for Immunology, Switzerland.
Rolink
A
A
Melchers
F
F
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000201:enzymology / Q000276:immunology*; D001483:Base Sequence; D002454:Cell Differentiation; D004254:DNA Nucleotidyltransferases / Q000172:deficiency*; D017931:DNA Primers / Q000235:genetics; D004268:DNA-Binding Proteins; D005260:Female; D015322:Gene Rearrangement, B-Lymphocyte; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000201:enzymology / Q000276:immunology*; D007145:Immunoglobulin kappa-Chains / Q000235:genetics*; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D011506:Proteins / Q000235:genetics / Q000276:immunology; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000276:immunology; D019253:Proto-Oncogene Proteins c-bcl-2; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics / Q000276:immunology; D014158:Transcription, Genetic; D045567:VDJ Recombinases
D017931:DNA Primers; D004268:DNA-Binding Proteins; D007145:Immunoglobulin kappa-Chains; D011506:Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; C499308:Rag2 protein, mouse; C064655:V(D)J recombination activating protein 2; D019009:Proto-Oncogene Proteins c-kit; D004254:DNA Nucleotidyltransferases; D045567:VDJ Recombinases