c-Myb Exacerbates Atherosclerosis Through Regulation of Harmful B2 and Protective IgM-producing Antibody Secreting Cells
26 Pages Posted: 5 Apr 2018 Sneak Peek Status: PublishedMore...
Inflammation plays a key role in the development of atherosclerosis, yet transcriptional regulators of the inflammatory process remain largely unknown. Here, we identify the nuclear transcription factor c-Myb as a crucial mediator of atherosclerotic disease. Using mice harboring a c-Myb hypomorphic allele (c-Mybh: M303V), we demonstrate that c-Myb potentiates atherosclerosis directly through its effects on B cell development. Reduced c-Myb activity, we show, associated with decreased numbers of harmful B2 cells at multiple tissue sites. Paradoxically, inhibiting c-Myb elevated levels of atheroprotective OxLDL specific IgM antibodies and increased numbers of IgM-producing antibody secreting cells (IgM-ASC), identifying a novel function for c-Myb in regulating T cell-independent natural antibody responses. Thus, targeted disruption of c-Myb signaling represents a potential therapeutic approach that circumvents key aspects of the complex biology of B cells in cardiovascular disease.
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