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

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 μ_s (μ-secreted). The 67K form correlates with the presence of surface IgM; thus it is designated μ_m (μ-membrane). Cells that make both forms of μ chain have two mRNAs, one of 2.4 kb that encodes μ_s and one of 2.7 kb that encodes μ_m. The difference between the μ_s and μ_m mRNAs can be localized to their 3′ ends by hybridizing ³²P-cDNA copies of the mRNA to a cloned copy of μ_s 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 μ_s 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: μ_m during the lymphocyte stages and μ_s during the secretion stages.