A new model of sheep Ig diversification: Shifting the emphasis toward combinatorial mechanisms and away from hypermutation

Craig N. Jenne, Laurie J. Kennedy, Peter McCullagh, John D. Reynolds*

*Corresponding author for this work

    Research output: Contribution to journalArticlepeer-review

    36 Citations (Scopus)

    Abstract

    The current model of Ig repertoire development in sheep focuses on the rearrangement of a small number (∼20) of Vλ gene segments. It is believed that this limited combinatorial repertoire is then further diversified through postrearrangement somatic hypermutation. This process has been reported to introduce as many as 110 mutations/1000 nucleotides. In contrast, our data have that indicated somatic hypermutation may diversify the preimmune repertoire to a much lesser extent. We have identified 64 new Vλ gene segments within the rearranged Ig repertoire. As a result, many of the unique nucleotide patterns thought to be the product of somatic hypermutation are actually hard-coded within the germline. We suggest that combinatorial rearrangement makes a much larger contribution, and somatic hypermutation makes a much smaller contribution to the generation of diversity within the sheep Ig repertoire than is currently acknowledged.

    Original languageEnglish
    Pages (from-to)3739-3750
    Number of pages12
    JournalJournal of Immunology
    Volume170
    Issue number7
    DOIs
    Publication statusPublished - 1 Apr 2003

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