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A New Model of Sheep Ig Diversification: Shifting the Emphasis Toward Combinatorial Mechanisms and Away from Hypermutation ¹

Craig N. Jenne^*, Laurie J. Kennedy^*, Peter McCullagh and John D. Reynolds^2,*

^* Immunology Research Group, University of Calgary, Calgary, Canada; Department of Molecular Medicine, John Curtin School of Medical Research, Australian National University, Canberra, Australia

The current model of Ig repertoire development in sheep focuses on the rearrangement of a small number (20) of V 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 V 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.

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The JI 2003 170: 3449-3450. [Full Text]  

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