c-Myb Exacerbates Atherosclerosis through Regulation of Protective IgM-Producing Antibody-Secreting Cells

Cell Rep. 2019 May 21;27(8):2304-2312.e6. doi: 10.1016/j.celrep.2019.04.090.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibody-Producing Cells / immunology*
  • Antibody-Producing Cells / metabolism
  • Atherosclerosis / genetics*
  • Atherosclerosis / immunology*
  • Atherosclerosis / pathology
  • Bone Marrow Cells / immunology
  • Bone Marrow Cells / pathology
  • Genes, myb
  • Immunoglobulin M / metabolism*
  • Male
  • Mice
  • Proto-Oncogene Proteins c-myb / genetics*
  • Proto-Oncogene Proteins c-myb / immunology*


  • Immunoglobulin M
  • Proto-Oncogene Proteins c-myb