Unexpected rearrangement and expression of the immunoglobulin lambda1 locus in scid mice.
In severe combined immunodeficient (scid) mice, V(D)J recombination is severely impaired due to a recessive mutation (scid). Thus, we were surprised to find in this study that Vlambda1-Jlambda1 rearrangement is routinely detectable in scid fetal liver, adult bone marrow, and spleen in the apparent absence of completed VH-DJH and Vkappa-Jkappa rearrangements. Particularly surprising, we found the level of Vlambda1-Jlambda1 rearrangement in scid fetal liver to be comparable to that in fetal liver of wild-type mice. The majority of scid Vlambda1-Jlambda1 rearrangements contained abnormal deletions at the VJ junction, consistent with the known effect of scid. However, approximately 15% of Vlambda1-Jlambda1 rearrangements lacked abnormal deletions. Productive lambda1 transcripts resulting from in-frame rearrangements were readily detectable in scid adult bone marrow and spleen, consistent with our ability to detect lambda1-expressing cells by flow cytometry in the spleens of bcl-2-transgenic scid mice. Strikingly, lambda1 transcripts from individual scid mice often showed VJ junctional sequences with the same recurring palindromic (P) additions of three, four, or five nucleotides. To account for these findings, we suggest that (a) nonhomologous end joining of Vlambda1 and Jlambda1 coding ends in fetal B lineage cells may not be (severely) impaired by scid; (b) recurring P additions in scid lambda1 transcripts may reflect certain molecular constraints imposed by scid on the resolution of Vlambda1 and Jlambda1 hairpin coding ends; and (c), scid lymphocytes with productively rearranged Vlambda1 and Jlambda1 elements may differentiate into recombinase-inactive cells and emigrate from bone marrow to spleen.
Ruetsch
N R
NR
Fox Chase Cancer Center, Institute for Cancer Research, Philadelphia, PA 19111, USA.
Bosma
G C
GC
Bosma
M J
MJ
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology; D001854:Bone Marrow Cells / Q000166:cytology; D005260:Female; D015870:Gene Expression; D015328:Gene Rearrangement, B-Lymphocyte, Light Chain; D006412:Hematopoietic Stem Cells / Q000166:cytology; D007133:Immunoglobulin Joining Region / Q000235:genetics*; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D007146:Immunoglobulin lambda-Chains / Q000235:genetics*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D016513:Mice, SCID; D019253:Proto-Oncogene Proteins c-bcl-2; D017384:Sequence Deletion; D013154:Spleen / Q000166:cytology
D007133:Immunoglobulin Joining Region; D007135:Immunoglobulin Variable Region; D007146:Immunoglobulin lambda-Chains; D019253:Proto-Oncogene Proteins c-bcl-2