Synthesis of secreted and membrane-bound immunoglobulin mu heavy chains is directed by mRNAs that differ at their 3′ ends

Frederick W. Alt, Alfred L.M. Bothwell, Michael Knapp, Edward Siden, Elizabeth Mather, Marian Koshland, David Baltimore

Research output: Contribution to journalArticlepeer-review

342 Scopus citations

Abstract

The mRNA isolated from B lymphocyte tumor cell lines directs synthesis of two forms of μ heavy chain, one with a molecular weight of 67K and one of 64K. When these cell lines are converted to IgM-secreting cells by fusion with a myeloma cell, the 64K form of μ predominates; thus it is designated μs (μ-secreted). The 67K form correlates with the presence of surface IgM; thus it is designated μm (μ-membrane). Cells that make both forms of μ chain have two mRNAs, one of 2.4 kb that encodes μs and one of 2.7 kb that encodes μm. The difference between the μs and μm mRNAs can be localized to their 3′ ends by hybridizing 32P-cDNA copies of the mRNA to a cloned copy of μs mRNA, treating the mixtures with SI nuclease, and resolving the nuclease-resistant duplexes by electrophoresis. By probing the separated species of RNA with a DNA copy of the 3′ untranslated region of μs mRNA, it was shown that the 3′ ends of the two μ mRNAs do not cross-hybridize. The difference between the two RNAs was mapped to the 3′ edge of the Cμ4 domain. Apparently two separate 3′ terminal sequences for μ mRNA are encoded in the genome, one that specifies an amino acid sequence appropriate for membrane-binding and a second that is involved in secretion. At different stages of immunocyte development, different μ mRNAs predominate: μm during the lymphocyte stages and μs during the secretion stages.

Original languageEnglish (US)
Pages (from-to)293-301
Number of pages9
JournalCell
Volume20
Issue number2
DOIs
StatePublished - Jun 1980
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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