The 3′ enhancer region determines the B/T specificity and pro-B/pre-B specificity of immunoglobulin Vκ-Jκ joining

Ryuji Hiramatsu, Kiwamu Akagi, Masao Matsuoka, Kunihiko Sakumi, Hiro Nakamura, Linda Kingsbury, Chella David, Richard R. Hardy, Ken ichi Yamamura, Hitoshi Sakano

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Abstract

Using transgenic substrates, we found that the immunoglobulin κ gene 3′ enhancer (E3′) acts as a negative regulator in Vκ-Jκ joining. Although the E3′ was originally identified as a transcriptional enhancer, it acts in a Buppressive manner for recombinational regulation. Base substitution analysis has shown that the PU. 1-binding site within the E3′ regulates the B/T specificity of Vκ-Jκ joining. In a substrate with a mutated PU. 1-binding site (GAGGAA to TCTTCG), Vκ-Jκ joining occurred not only in B cells, but also in T cells. The E3′ region is also responsible for determining the pro-B/pre-B specificity of Vκ-Jκ joining. When the E3′ region was deleted, κ gene rearrangement actively occurred at the early pro-B stage of B cell development: non-germline (N) nucleotides were common at recombination junctions.

Original languageEnglish
Pages (from-to)1113-1123
Number of pages11
JournalCell
Volume83
Issue number7
DOIs
Publication statusPublished - Dec 29 1995
Externally publishedYes

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All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

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