Frequent aberrant immunoglobulin gene rearrangements in pro-B cells revealed by a bcl-xL transgene.
During B lymphocyte development, pro-B cells that fail to rearrange an immunoglobulin heavy (IgH) chain allele productively are thought to undergo developmental arrest and death, but because these cells are short-lived in vivo they are not well characterized. Transgenic mice expressing the apoptosis regulatory gene bcl-xL in the B lineage developed large expansions of pro-B cells in bone marrow. V(D)J rearrangements in the expanded populations were nearly all nonproductive, and DJH rearrangements were enriched for joints in DH reading frame 2 and for aberrant joints with extensive DH or JH deletions. Thus, the death of pro-B cells with failed immunoglobulin rearrangements occurs by apoptosis, and bcl-xL can deliver a strong survival signal at the pro-B stage. This analysis also demonstrated that immunoglobulin gene rearrangement is less precise than previously appreciated.
Fang
W
W
Department of Medicine, University of Minnesota Medical School, Minneapolis 55455, USA.
Mueller
D L
DL
Pennell
C A
CA
Rivard
J J
JJ
Li
Y S
YS
Hardy
R R
RR
Schlissel
M S
MS
Behrens
T W
TW
D000818:Animals; D017209:Apoptosis / Q000235:genetics; D016175:B-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D001483:Base Sequence; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002470:Cell Survival / Q000235:genetics / Q000276:immunology; D015322:Gene Rearrangement, B-Lymphocyte / Q000276:immunology*; D005803:Genes, Immunoglobulin / Q000276:immunology*; D008213:Lymphocyte Activation / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D011519:Proto-Oncogenes / Q000276:immunology*; D013234:Stem Cells / Q000378:metabolism*; D019076:Transgenes / Q000276:immunology*