c-Myb Exacerbates Atherosclerosis through Regulation of Protective IgM-Producing Antibody-Secreting Cells Academic Article uri icon

  •  
  • Overview
  •  
  • Research
  •  
  • Identity
  •  
  • Additional Document Info
  •  
  • View All
  •  

abstract

  • Mechanisms that govern transcriptional regulation of inflammation in atherosclerosis remain largely unknown. Here, we identify the nuclear transcription factor c-Myb as an important mediator of atherosclerotic disease in mice. Atherosclerosis-prone animals fed a diet high in cholesterol exhibit increased levels of c-Myb in the bone marrow. Use of mice that either harbor a c-Myb hypomorphic allele or where c-Myb has been preferentially deleted in B cell lineages revealed that c-Myb potentiates atherosclerosis directly through its effects on B lymphocytes. Reduced c-Myb activity prevents the expansion of atherogenic B2 cells yet associates with increased numbers of IgM-producing antibody-secreting cells (IgM-ASCs) and elevated levels of atheroprotective oxidized low-density lipoprotein (OxLDL)-specific IgM antibodies. Transcriptional profiling revealed that c-Myb has a limited effect on B cell function but is integral in maintaining B cell progenitor populations in the bone marrow. Thus, targeted disruption of c-Myb beneficially modulates the complex biology of B cells in cardiovascular disease.

authors

  • Shikatani, Eric A
  • Besla, Rickvinder
  • Ensan, Sherine
  • Upadhye, Aditi
  • Khyzha, Nadiya
  • Li, Angela
  • Emoto, Takuo
  • Chiu, Felix
  • Degousee, Norbert
  • Moreau, Joshua M
  • Perry, Heather M
  • Thayaparan, Danya
  • Cheng, Henry S
  • Pacheco, Shaun
  • Smyth, David
  • Noyan, Hossein
  • Zavitz, Cale
  • Bauer, Carla MT
  • Hilgendorf, Ingo
  • Libby, Peter
  • Swirski, Filip K
  • Gommerman, Jennifer L
  • Fish, Jason E
  • Stampfli, Martin R
  • Cybulsky, Myron I
  • Rubin, Barry B
  • Paige, Christopher J
  • Bender, Timothy P
  • McNamara, Coleen A
  • Husain, Mansoor
  • Robbins, Clinton S

publication date

  • May 2019