The catalytic domain of the histone methyltransferase NSD2/MMSET is required for the generation of B1 cells in mice.

Autor: Dobenecker MW; Laboratory of Immune Cell Epigenetics and Signaling, Rockefeller University, New York, NY, USA.; Bristol-Meyers Squibb, Princeton, NJ, USA., Marcello J; Laboratory of Immune Cell Epigenetics and Signaling, Rockefeller University, New York, NY, USA., Becker A; Laboratory of Immune Cell Epigenetics and Signaling, Rockefeller University, New York, NY, USA.; Departments of Pediatrics, Cell and Developmental Biology, Weill Cornell Medical College, New York, NY, USA., Rudensky E; Laboratory of Immune Cell Epigenetics and Signaling, Rockefeller University, New York, NY, USA.; NYU Langone Medical Center and School of Medicine, New York, NY, USA., Bhanu NV; Penn Epigenetics Institute, Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Carrol T; Bioinformatics Resource Center, Rockefeller University, New York, NY, USA., Garcia BA; Penn Epigenetics Institute, Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Prinjha R; Epinova DPU, Immuno-Inflammation Therapy Area, GlaxoSmithKline R&D, Stevenage, UK., Yurchenko V; Laboratory of Immune Cell Epigenetics and Signaling, Rockefeller University, New York, NY, USA.; Sechenov First Moscow State Medical University, Moscow, Russia.; Life Science Research Centre, University of Ostrava, Ostrava, Czech Republic., Tarakhovsky A; Laboratory of Immune Cell Epigenetics and Signaling, Rockefeller University, New York, NY, USA.
Jazyk: angličtina
Zdroj: FEBS letters [FEBS Lett] 2020 Oct; Vol. 594 (20), pp. 3324-3337. Date of Electronic Publication: 2020 Aug 29.
DOI: 10.1002/1873-3468.13903
Abstrakt: Humoral immunity in mammals relies on the function of two developmentally and functionally distinct B-cell subsets-B1 and B2 cells. While B2 cells are responsible for the adaptive response to environmental antigens, B1 cells regulate the production of polyreactive and low-affinity antibodies for innate humoral immunity. The molecular mechanism of B-cell specification into different subsets is understudied. In this study, we identified lysine methyltransferase NSD2 (MMSET/WHSC1) as a critical regulator of B1 cell development. In contrast to its minor impact on B2 cells, deletion of the catalytic domain of NSD2 in primary B cells impairs the generation of B1 lineage. Thus, NSD2, a histone H3 K36 dimethylase, is the first-in-class epigenetic regulator of a B-cell lineage in mice.
(© 2020 Federation of European Biochemical Societies.)
Databáze: MEDLINE
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