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Nucleic Acids Research, 1987, Vol. 15, No. 11 4603-4615
© 1987

Articles

Regulation of differential processing of mouse immunoglobulin µ heavy-chain mRNA

Naoya Tsurushita, Nevenka M. Avdalovic* and Laurence Jay Korn*

Department of Genetics, Stanford University School of Medicine Stanford, CA 94305, USA

Received March 4, 1987. Revised April 29, 1987. Accepted April 29, 1987.

The switch between the synthesis of membrane-bound and secreted IgH during B cell differentiation is accomplished by producing, from a single gene, two alternative forms of µ heavy-chain mRNA that differ only in their 3' termini. The precursor µ RNA is either polyadenylated at the first poly(A) site, for secreted µ mRNA, or spliced between the C4 and M1 exons, for membrane-bound µ mRNA, in a mutually exclusive manner. To elucidate the molecular mechanism of the differential processing of mouse µ mRNA, we analyzed the expression of various mouse µ gene constructs stably transfected into mouse cell lines. In B cell lines, processing of the exogenously transfected µ gene transcripts accurately reflected the developmental stage of the recipient cells: both secreted and membrane-bound µ mRNAs are produced in early-stage B cells while secreted µ mRNA is primarily produced in late-stage B cells. In fibroblast cell lines, µ mRNAs transcribed from the Moloney murine sarcoma virus LTR promoter were processed primarily to the secreted form. Thus, production of the secreted form seems to be the non-regulated processing pattern. When the splicing signal of the C4-M1 intron was mutagenized, polyadenylation at the first poly(A) site occurred efficiently regardless of the recipient cell lines. On the other hand, when the polyadenylation signal was mutagenized, the splicing occurred efficiently in early-stage B cells, but only weakly in late-stage B cells and fibroblast cells. These results suggest that the splicing of the C4-M1 intron is stimulated in early-stage B cells.

*Present address: Protein Design Labs, 3181 Porter Drive, Palo Alto, CA 94304, USA


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