DH element reading frame selection is influenced by an Ig heavy chain transgene, but not by bcl-2

David Tarlinton, Andreas Strasser, Michelle McLean, Antony Basten

Research output: Contribution to journalArticleResearchpeer-review

6 Citations (Scopus)


Mouse B cell precursors containing Ig DHJH junctions in one particular reading frame are selectively lost during B cell development. In this register, arbitrarily referred to as reading frame 2, DHJH junctions give rise to an open reading frame starting upstream of the DH element and including the DHJH-peptide fused to the constant region of IgM. Expression of this protein, called Dμ, has been strongly implicated in the loss of B cell precursors containing reading frame 2 DHJH junctions. In an attempt to elucidate the means of Dμ counterselection, we have examined the reading frame distribution of DHJH junctions in peripheral B cells from mice transgenic for either the human bcl-2 oncogene or for a functionally rearranged Ig μ heavy chain. In bcl-2 transgenic mice, reading frame 2 accounted for <5% of the DHJH junctions in peripheral B cells, a value not significantly different from controls. Reading frames 1 and 3 were equally represented among the remaining junctions. By contrast, the reading frame distribution of endogenous DHJH junctions in splenic B cells from Ig μ heavy chain transgenic mice showed no evidence of bias against Dμ encoding DHJH junctions. Reading frames 2 and 3 accounted for 27% and 30% of the sequenced DHJH junctions, respectively, and the remaining 43% were reading frame 1. Thus although the presence of BCL-2 cannot prevent the selective loss of reading frame 2 DHJH B cells, a functional μ heavy chain can. These results suggest that Dμ-expressing B cell precursors may be selectively lost because of the premature and inappropriate cessation of heavy chain gene rearrangement rather than because of the induction of an apoptotic process which can be blocked by BCL-2.

Original languageEnglish
Pages (from-to)3341-3350
Number of pages10
JournalJournal of Immunology
Issue number7
Publication statusPublished - 1 Dec 1995

Cite this