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Histone methyltransferase MMSET/NSD2 is essential for generation of B1 cell compartment in mice

View ORCID ProfileMarc-Werner Dobenecker, Vyacheslav Yurchenko, Jonas Marcello, Annette Becker, Eugene Rudensky, Natarajan V. Bahnu, Thomas Carrol, Benjamin A. Garcia, Brad R. Rosenberg, Rabinder Prinjha, Alexander Tarakhovsky
doi: https://doi.org/10.1101/687806
Marc-Werner Dobenecker
1Laboratory of Immune Cell Epigenetics and Signaling, Rockefeller University, New York, NY, USA
2Now Bristol-Meyers Squibb, Princeton, New Jersey, NJ, USA
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  • ORCID record for Marc-Werner Dobenecker
  • For correspondence: tarakho@rockefeller.edu Marc-Werner.Dobenecker@BMS.com
Vyacheslav Yurchenko
1Laboratory of Immune Cell Epigenetics and Signaling, Rockefeller University, New York, NY, USA
3Now Life Science Research Centre, University of Ostrava, Czech Republic
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Jonas Marcello
1Laboratory of Immune Cell Epigenetics and Signaling, Rockefeller University, New York, NY, USA
4Now Centogene AG, Rostock, Germany
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Annette Becker
1Laboratory of Immune Cell Epigenetics and Signaling, Rockefeller University, New York, NY, USA
5Now Arcus Biosciences, Hayward, CA, USA
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Eugene Rudensky
1Laboratory of Immune Cell Epigenetics and Signaling, Rockefeller University, New York, NY, USA
6Now NYU School of Medicine, New York, NY, USA
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Natarajan V. Bahnu
7Epigenetics Program, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
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Thomas Carrol
8Bioinformatics Resource Center, Rockefeller University, New York, NY, USA
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Benjamin A. Garcia
7Epigenetics Program, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
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Brad R. Rosenberg
9Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
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Rabinder Prinjha
10Epinova DPU, Immuno-Inflammation Therapy Area, GlaxoSmithKline R&D, Stevenage, UK
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Alexander Tarakhovsky
1Laboratory of Immune Cell Epigenetics and Signaling, Rockefeller University, New York, NY, USA
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  • For correspondence: tarakho@rockefeller.edu Marc-Werner.Dobenecker@BMS.com
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Abstract

Humoral immunity in mice and man relies on the function of two developmentally and functionally distinct B cell subsets - B1 and B2 cells. While B2 cells are responsible for most of the adaptive response to environmental antigens, B1 cells, which are comprised of phenotypically distinct B1a and B1b cells, are carriers of the innate humoral immunity that relies on production of poly-reactive and low affinity antibodies. The molecular mechanism of B cell specification into different subsets is not well established. Here we identified lysine methyltransferase MMSET/NSD2 as a critical regulator of the B1 cell population. We show that NSD2 deficiency in B cell precursors prevents generation of the B1 cell compartment, while having a minor impact on B2 cells. Our data revealed MMSET/NSD2, which catalyzes histone H3 lysine 36 di-methylation, as the first in class epigenetic master regulator of a major B cell lineage in mice.

Footnotes

  • Abbreviations: B cell receptor (BCR), histone 3 lysine 36 di-methylation (H3K36me2), nuclear receptor SET domain-containing (NSD2)

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted July 02, 2019.
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Histone methyltransferase MMSET/NSD2 is essential for generation of B1 cell compartment in mice
Marc-Werner Dobenecker, Vyacheslav Yurchenko, Jonas Marcello, Annette Becker, Eugene Rudensky, Natarajan V. Bahnu, Thomas Carrol, Benjamin A. Garcia, Brad R. Rosenberg, Rabinder Prinjha, Alexander Tarakhovsky
bioRxiv 687806; doi: https://doi.org/10.1101/687806
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Histone methyltransferase MMSET/NSD2 is essential for generation of B1 cell compartment in mice
Marc-Werner Dobenecker, Vyacheslav Yurchenko, Jonas Marcello, Annette Becker, Eugene Rudensky, Natarajan V. Bahnu, Thomas Carrol, Benjamin A. Garcia, Brad R. Rosenberg, Rabinder Prinjha, Alexander Tarakhovsky
bioRxiv 687806; doi: https://doi.org/10.1101/687806

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