Mechanism of class switching.
We have documented the action of unequal sister chromatid exchange on antibody genes, and our studies provide the first molecular description of an unequal sister chromatid exchange event. We delineated the sequences that mediate class switch recombination in normal B cells through genomic Southern analysis of five IgG2-producing hybridomas. Successive subclass switching was documented in two of eight maps and may possibly account for interposed DNA in three additional maps, implying that subclass switching may be a relatively frequent occurrence in normal B cells. As in most other myelomas and hybridomas, the 5' breakpoint of switch recombination in our panel of hybridomas falls 5' to Cmu-associated tandem repeats, whereas the 3' breakpoint falls within C gamma-associated tandem repeats. We consider various hypotheses in the text, the most interesting of which is that deletion of Cmu-associated tandem repeats is a necessary first step before class switch recombination in mature B cells. This hypothesis suggests that Cmu-associated tandem repeats may be a separately regulated DNA element.
Birshtein
B K
BK
Department of Cell Biology, Albert Einstein College of Medicine, Bronx, New York 10461.
Katzenberg
D R
DR
Weinreb
A
A
Giannini
S
S
Bard
J
J
Calvo
C F
CF
Martinez
N
N
D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism* / Q000502:physiology; D007132:Immunoglobulin Isotypes / Q000096:biosynthesis*; D051379:Mice; D011995:Recombination, Genetic
D007132:Immunoglobulin Isotypes