Development of B cells in scid mice with immunoglobulin transgenes: implications for the control of V(D)J recombination.
The inability of scid pro-B cells to progress to the pre-B and B cell stages is believed to be caused by a defective recombinase activity that fails to resolve chromosomal breaks resulting from attempted V(D)J recombination. In support of this model, we report that certain immunoglobulin transgenes, specifically those which strongly inhibit endogenous VH-to-DJH and V kappa-to-J kappa rearrangement in wild-type mice, allow scid pro-B cells to progress to the pre-B and B cell stages. This rescue of scid B cell differentiation is associated with a dramatic reduction in expression of the recombination activation genes, RAG1 and RAG2, and with reduced transcription of the kappa locus.
Chang
Y
Y
Fox Chase Cancer Center, Institute for Cancer Research, Philadelphia, Pennsylvania 19111, USA.
Bosma
G C
GC
Bosma
M J
MJ
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D001483:Base Sequence; D004268:DNA-Binding Proteins; D005434:Flow Cytometry; D015322:Gene Rearrangement, B-Lymphocyte / Q000235:genetics*; D018398:Homeodomain Proteins; D007133:Immunoglobulin Joining Region / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000235:genetics; D007138:Immunoglobulin delta-Chains / Q000235:genetics; D008213:Lymphocyte Activation / Q000235:genetics; D051379:Mice; D016513:Mice, SCID; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis; D011995:Recombination, Genetic; D014158:Transcription, Genetic
D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D007133:Immunoglobulin Joining Region; D007135:Immunoglobulin Variable Region; D007138:Immunoglobulin delta-Chains; D012333:RNA, Messenger; C499308:Rag2 protein, mouse; C064655:V(D)J recombination activating protein 2; C064658:RAG-1 protein