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Antibody repertoire diversification through VH gene replacement in mice cloned from an IgA plasma cell.

Proceedings of the National Academy of Sciences of the United States of America (2015-01-23)
Rashmi Kumar, Martina P Bach, Federica Mainoldi, Mikako Maruya, Satoshi Kishigami, Hassan Jumaa, Teruhiko Wakayama, Osami Kanagawa, Sidonia Fagarasan, Stefano Casola
ABSTRACT

In mammals, VDJ recombination is responsible for the establishment of a highly diversified preimmune antibody repertoire. Acquisition of a functional Ig heavy (H) chain variable (V) gene rearrangement is thought to prevent further recombination at the IgH locus. Here, we describe VHQ52(NT); Vκgr32(NT) Ig monoclonal mice reprogrammed from the nucleus of an intestinal IgA(+) plasma cell. In VHQ52(NT) mice, IgA replaced IgM to drive early B-cell development and peripheral B-cell maturation. In VHQ52(NT) animals, over 20% of mature B cells disrupted the single productive, nonautoimmune IgH rearrangement through VH replacement and exchanged it with a highly diversified pool of IgH specificities. VH replacement occurred in early pro-B cells, was independent of pre-B-cell receptor signaling, and involved predominantly one adjacent VH germ-line gene. VH replacement was also identified in 5% of peripheral B cells of mice inheriting a different productive VH rearrangement expressed in the form of an IgM H chain. In summary, editing of a productive IgH rearrangement through VH replacement can account for up to 20% of the IgH repertoire expressed by mature B cells.

MATERIALS
Product Number
Brand
Product Description

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