Structure and expression of germline immunoglobulin gamma 3 heavy chain gene transcripts: implications for mitogen and lymphokine directed class-switching.
We have characterized the structure and expression of transcripts synthesized from the murine germline immunoglobulin gamma 3 heavy chain gene in certain B-lineage cells. The transcripts initiate upstream of the switch gamma 3 region, generating a 5' exon that is spliced to C gamma 3 exons. Expression of this germline transcript is induced when splenic B cells or A-MuLV-transformed pre-B cell lines are cultured in the presence of lipopolysaccharide (LPS). Addition of interleukin-4 (IL-4) to these lipopolysaccharide (LPS) cultures dramatically inhibits induction of the germline gamma 3 transcript. Induction of germline gamma 3 transcripts occurs before the increased accumulation of gamma 3-producing cells and VDJ-gamma 3 mRNA in cultures of splenic B cells. These data provide further evidence that germline CH transcriptional units are important components in the regulation of heavy chain class-switching. In addition, the pre-B cell lines that we describe represent the first example of permanent cell lines that regulate expression of the germline gamma locus in response to LPS plus IL-4 treatment in a manner analogous to normal B cells; therefore these lines should represent an excellent model system to further study the molecular mechanisms by which germline expression is regulated by these agents.
Rothman
P
P
Howard Hughes Medical Institute, College of Physicians and Surgeons, Columbia University, New York, NY 10032.
Lutzker
S
S
Gorham
B
B
Stewart
V
V
Coffman
R
R
Alt
F W
FW
D000818:Animals; D000916:Antibody Diversity; D001483:Base Sequence; D004247:DNA / Q000235:genetics*; D005786:Gene Expression Regulation; D005803:Genes, Immunoglobulin; D005812:Genes, Switch; D007142:Immunoglobulin gamma-Chains / Q000235:genetics*; D015847:Interleukin-4 / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008969:Molecular Sequence Data; D014158:Transcription, Genetic
D007142:Immunoglobulin gamma-Chains; D008070:Lipopolysaccharides; D015847:Interleukin-4; D004247:DNA