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

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

Supelco
4-Hydroxytamoxifen, analytical standard, (E) and (Z) isomers (50:50)
Sigma-Aldrich
β-D-Allose, rare aldohexose sugar
Sigma-Aldrich
4-Hydroxytamoxifen, ≥70% Z isomer (remainder primarily E-isomer)
Supelco
4-Hydroxytamoxifen, (E) and (Z) isomers (50:50), analytical standard