Molecular characterization of human Ig heavy chain DIR genes

Iñaki Sanz, Shou Shu Wang, Georgina Meneses, Michael Fischbach

Research output: Contribution to journalArticlepeer-review

31 Scopus citations


Antibody VDJ recombination is ensured by evolutionarily conserved recombination signals (RS). The T2/23 rule postulates that only gene segments with asymmetrically spaced RS recombine with one another. Two unusually long D genes (170 bp) with irregular RS (DIR) have been reported in humans and have been postulated to participate actively in VDJ recombination, thus frequently contributing to the Ab heavy chain third hypervariable region (CDR3). However, the limited sequence information retained in the CDR3 along with significant sequence diversity has precluded an accurate assessment of the actual role and genomic diversity of DIR genes. Furthermore, DIR genes pose an interesting puzzle in terms of their precise mechanism of recombination because they possess multiple and imperfect RS, often located up to 30 bp away from the recombining fragment within the DIR coding region. Here we present conclusive evidence for the existence of additional human germ-line DIR genes and preliminary evidence that suggests the absence of DIR-like sequences in nonprimate animals. We also show that DIR genes are under the transcriptional control of V(H)-independent promoters and have the potential to encode a Dμ protein of 105 amino acids. Finally, DIR genes seem at least in early fetal life to recombine preferentially through the conventional 3' RS.

Original languageEnglish (US)
Pages (from-to)3958-3969
Number of pages12
JournalJournal of Immunology
Issue number8
StatePublished - Apr 15 1994
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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