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

作者：Kumar Rashmi; Bach P; Mainoldi Federica; Maruya Mikako; Kishigami Satoshi; Jumaa Hassan; Wakayama Teruhiko; Kanagawa Osami; Fagarasan Sidonia; Casola Stefano^*

来源：Proceedings of the National Academy of Sciences of the United States of America, 2015, 112(5): E450-E457.

DOI：10.1073/pnas.1417988112

• B cells
• VH replacement
• antibody repertoire
• IgA
• nuclear cloning

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 V(H)Q52(NT); V kappa gr32(NT) Ig monoclonal mice reprogrammed from the nucleus of an intestinal IgA(+) plasma cell. In V(H)Q52(NT) mice, IgA replaced IgM to drive early B-cell development and peripheral B-cell maturation. In V(H)Q52(NT) animals, over 20% of mature B cells disrupted the single productive, non-autoimmune 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.

• 出版日期2015-2-3
• 单位RIKEN