PT  - JOURNAL ARTICLE
AU  - Dobenecker, Marc-Werner
AU  - Yurchenko, Vyacheslav
AU  - Marcello, Jonas
AU  - Becker, Annette
AU  - Rudensky, Eugene
AU  - Bahnu, Natarajan V.
AU  - Carrol, Thomas
AU  - Garcia, Benjamin A.
AU  - Rosenberg, Brad R.
AU  - Prinjha, Rabinder
AU  - Tarakhovsky, Alexander
TI  - Histone methyltransferase MMSET/NSD2 is essential for generation of B1 cell compartment in mice
AID  - 10.1101/687806
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 687806
4099  - http://biorxiv.org/content/early/2019/07/02/687806.short
4100  - http://biorxiv.org/content/early/2019/07/02/687806.full
AB  - 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.