A class switch control region at the 3' end of the immunoglobulin heavy chain locus.
We replaced the IgH 3' enhancer (3'EH) region with a neomycin resistance gene in ES cells and generated chimeric mice in which all mature lymphocytes were either heterozygous (3'EH+/-) or homozygous (3'EH-/-) for the mutation. In vitro activated 3'EH-/- B cells responded similarly to 3'EH+/- B cells with respect to proliferation and secretion of IgM and IgG1 but were specifically deficient in IgG2a, IgG2b, IgG3, and IgE secretion. These isotype deficiencies correlated with a deficiency in accumulation of transcripts from and class switching to affected CH genes. In vivo, chimeric mice containing only 3'EH-/- B cells were deficient in serum IgG2a and IgG3. We propose that the 3'EH-/- mutation disrupts the activity of a regulatory region that influences heavy chain class switching to several different CH genes that lie as far as 100 kb upstream of the mutation.
Cogné
M
M
Howard Hughes Medical Institute, Children's Hospital, Boston, Massachusetts.
Lansford
R
R
Bottaro
A
A
Zhang
J
J
Gorman
J
J
Young
F
F
Cheng
H L
HL
Alt
F W
FW
D000818:Animals; D002678:Chimera; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain; D005803:Genes, Immunoglobulin; D005812:Genes, Switch; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D007132:Immunoglobulin Isotypes / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D010641:Phenotype; D015183:Restriction Mapping; D014158:Transcription, Genetic
D007143:Immunoglobulin Heavy Chains; D007132:Immunoglobulin Isotypes