Transcripts of the immunoglobulin C mu gene vary in structure and splicing during lymphoid development

Abstract

Two classes of transcripts of the mouse immunoglobulin mu constant region (C mu) gene can be distinguished. Whereas B cells contain mu mRNAs of 2.4 and 2.7 kilobases (kb), many T lymphoma, Abelson pre-B lymphoma, and myeloid tumor cell lines contain polyadenylylated RNA species bearing C mu sequences (C mu RNAs) of 1.9, 2.1, 2.3, and 3.0 kb. Production of C mu RNAs, unlike mu mRNAs, does not require recombination with the joining region (JH) locus. To define the structure of C mu RNAs, RNA from representative cell lines was fractionated by gel electrophoresis, transferred to diazobenzyloxymethyl paper, and tested for hybridization with 23 DNA fragments that collectively span a chromosomal mu gene, cloned from a plasmacytoma. All the C mu RNAs bear sequences derived from each of the four C mu domains, but none contain the intervening sequences separating domains; thus each represents a spliced RNA species. The 1.9-kb C mu RNA contains the 3' sequence characteristic of secreted mu chain, whereas the longer species bear that of membrane-bound mu chin. Hence C mu RNAs and mu mRNAs are equivalent throughout the C mu and 3' terminal regions. They differ markedly, however, in their 5' regions, because the 3.0-and 2.3-kb C mu RNAs bear sequences from within the conventional JH-C mu intervening sequence. Because these sequences are several kb from C mu, this region must contain at least one hitherto unsuspected splice site. C mu RNAs may not express immunological diversity, because no evidence was found that they bear variable regions. T and pre-B lymphoid and myeloid cells contain equivalent C mu RNA species, which coexist with mu mRNAs in some pre-B and B lymphoid lines. C mu RNA expression appears to reflect an activated state of the C mu gene common to cells at early stages of T, B, and myeloid development.