B cells support the repair of injured tissues by adopting MyD88-dependent regulatory functions and phenotype

FASEB J. 2021 Dec;35(12):e22019. doi: 10.1096/fj.202101095RR.


Exogenously applied mature naïve B220+ /CD19+ /IgM+ /IgD+ B cells are strongly protective in the context of tissue injury. However, the mechanisms by which B cells detect tissue injury and aid repair remain elusive. Here, we show in distinct models of skin and brain injury that MyD88-dependent toll-like receptor (TLR) signaling through TLR2/6 and TLR4 is essential for the protective benefit of B cells in vivo, while B cell-specific deletion of MyD88 abrogated this effect. The B cell response to injury was multi-modal with simultaneous production of both regulatory cytokines, such as IL-10, IL-35, and transforming growth factor beta (TGFβ), and inflammatory cytokines, such as tumor necrosis factor alpha (TNFα), IL-6, and interferon gamma. Cytometry analysis showed that this response was time and environment-dependent in vivo, with 20%-30% of applied B cells adopting an immune modulatory phenotype with high co-expression of anti- and pro-inflammatory cytokines after 18-48 h at the injury site. B cell treatment reduced the expression of TNFα and increased IL-10 and TGFβ in infiltrating immune cells and fibroblasts at the injury site. Proteomic analysis further showed that B cells have a complex time-dependent homeostatic effect on the injured microenvironment, reducing the expression of inflammation-associated proteins, and increasing proteins associated with proliferation, tissue remodeling, and protection from oxidative stress. These findings chart and validate a first mechanistic understanding of the effects of B cells as an immunomodulatory cell therapy in the context of tissue injury.

Keywords: B cells; MyD88; TLR; immunomodulation; injury; regulatory mechanisms.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B-Lymphocytes / physiology*
  • Brain Injuries / etiology
  • Brain Injuries / metabolism
  • Brain Injuries / pathology
  • Brain Injuries / prevention & control*
  • Cytokines / metabolism*
  • Interleukin-10 / physiology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Myeloid Differentiation Factor 88 / physiology*
  • Phenotype
  • Signal Transduction
  • Skin / immunology*
  • Skin / injuries
  • Skin / metabolism
  • Toll-Like Receptors / metabolism
  • Tumor Necrosis Factor-alpha / metabolism
  • Wound Healing*


  • Cytokines
  • IL10 protein, mouse
  • Myd88 protein, mouse
  • Myeloid Differentiation Factor 88
  • Toll-Like Receptors
  • Tumor Necrosis Factor-alpha
  • Interleukin-10