Normal recombination substrate VH to DJH rearrangements in pre-B cell lines from scid mice.
To further analyze the VDJ recombination defect in lymphoid pre-B cells from mice with severe combined immune deficiency (scid mice), we have assayed the ability of Abelson murine leukemia virus (A-MuLV) transformed pre-B cells from scid mice to rearrange a recombination substrate in which inverted VH to DJH joins activate a selectable (gpt) gene. In unselected populations, substrate rearrangements occurred frequently, but were aberrant and probably analogous to the aberrant rearrangements observed at endogenous scid Ig gene loci. In contrast, populations of scid pre-B lines selected for gpt activity within the substrate contained mostly "normal" VH to DJH joins within the introduced substrate. These findings demonstrate that scid pre-B cells can make normal joins at low efficiency and are discussed with respect to the potential mechanism of the scid defect and the occurrence of Igs in leaky scid mice.
Ferrier
P
P
Howard Hughes Medical Institute, College of Physicians and Surgeons of Columbia University, New York, New York 10032.
Covey
L R
LR
Li
S C
SC
Suh
H
H
Malynn
B A
BA
Blackwell
T K
TK
Morrow
M A
MA
Alt
F W
FW
D000011:Abelson murine leukemia virus; D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology*; D001483:Base Sequence; D002460:Cell Line; D002472:Cell Transformation, Viral; D003001:Cloning, Molecular; D004247:DNA; D005786:Gene Expression Regulation; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain / Q000235:genetics*; D006412:Hematopoietic Stem Cells / Q000166:cytology; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007144:Immunoglobulin J-Chains / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D007138:Immunoglobulin delta-Chains / Q000235:genetics; D007153:Immunologic Deficiency Syndromes / Q000235:genetics / Q000276:immunology; D051379:Mice; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction
D007143:Immunoglobulin Heavy Chains; D007144:Immunoglobulin J-Chains; D007135:Immunoglobulin Variable Region; D007138:Immunoglobulin delta-Chains; D004247:DNA