Structure and expression of germline immunoglobulin γ³ heavy chain gene transcripts: Implications for mitogen and lymphokine directed class-switching

We have characterized the structure and expression of transcripts synthesized from the murlne germline immunoglobulin γ³ heavy chain gene In certain B-llneage cells. The transcripts initiate upstream of the switch γ³ region, generating a 5' exon that is spliced to Cγ3 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 lipopoiysaccharide (LPS). Addition of lnterleukln_-4 (IL_-4) to these lipopoiysaccharide (LPS) cultures dramatically Inhibits Induction of the germline γ³ transcript. Induction of germline γ3 transcripts occurs before the Increased accumulation of 73-produclng cells and VDJγ_-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 7 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.