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

Abstract

Immunoglobulin VDJ recombination is associated with transcriptional activation of the Ig variable region elements. We have previously described a novel Ig g 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 ofa 5' leader sequence spliced to Cg (LS-Cjz)

Evidence for failure of V(D)J recombination in bone marrow pre-B cells from X-linked agammaglobulinemia.

“…PCR were performed as described previously (15). The PCR blots were probed with the 1.6-kb CM cDNA insert from the plasmid puHM2 (18).…”

“…Transcription of unrearranged VH gene elements and DJH intermediate structures occurs in close correlation with VH to DJH recombination (13,14). Germ line transcriptional activation of the JHlocus precedes D to JH recombination (14,15), and activation of the JKlocus precedes VK to JK recombination (16). Similar transcriptional activation occurs in recombination of the elements of the T cell antigen receptor (17).…”

“…Germ line transcripts, composed of a leader sequence (LS) spliced to the constant region of u chain (Cu), were produced by a limited number of pre-B cell hybrids derived from normal fetal liver, indicating that LS-Cu was a product of normal pre-B cell development. LS-CAu is the product ofan LS exon that is [14][15][16] kb upstream of the JH locus (15). Transcription from the LS exon provides transcriptional activation of the JH locus.…”