Germ line transcription of the immunoglobulin heavy chain locus directs production of mu chain without VDJ.

Immunoglobulin VDJ recombination is associated with transcriptional activation of the Ig variable region elements. We have previously described a novel Ig mu chain protein and mRNA produced by pre-B cell hybrids from normal and X-linked agammaglobulinemic bone marrow. We have now characterized the mRNA encoding this protein and find that it is composed of a 5' leader sequence spliced to C mu (LS-C mu), lacking the variable (V), diversity (D), and joining (J) gene sequences. The leader sequence is encoded by a novel exon 16 kb upstream of the JH locus. Transcription of the germ line heavy chain locus from this LS exon results in transcriptional activation of the JH locus, apparently the initial step in commitment to B lymphoid development. Polymerase chain reaction amplification of normal bone marrow shows that these germ line LS-C mu transcripts are a product of bone marrow pre-B cells. Production of LS-C mu commences a sequential process of transcriptional activation, with concordant translation of Ig rearrangement intermediates, in the process of creating a productive VDJ rearrangement.