Natural Killer-like B Cells Prime Innate Lymphocytes against Microbial Infection

Immunity. 2016 Jul 19;45(1):131-44. doi: 10.1016/j.immuni.2016.06.019. Epub 2016 Jul 12.

Abstract

Natural killer (NK) cells and non-cytotoxic interferon-γ (IFN-γ)-producing group I innate lymphoid cells (ILC1s) produce large amounts of IFN-γ and cause activation of innate and adaptive immunity. However, how NKs and ILC1s are primed during infection remains elusive. Here we have shown that a lymphocyte subpopulation natural killer-like B (NKB) cells existed in spleen and mesenteric lymph nodes (MLNs). NKBs had unique features that differed from T and B cells, and produced interleukin-18 (IL-18) and IL-12 at an early phase of infection. NKB cells played a critical role in eradication of microbial infection via secretion of IL-18 and IL-12. Moreover, IL-18 deficiency abrogated the antibacterial effect of NKBs. Upon bacterial challenge, NKB precursors (NKBPs) rapidly differentiated to NKBs that activated NKs and ILC1s against microbial infection. Our findings suggest that NKBs might be exploited to develop effective therapies for treatment of infectious diseases.

Keywords: IL-18; ILC1s; NK cells; NKB cells; innate immunity.

MeSH terms

  • Animals
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / microbiology
  • Cell Differentiation
  • Cells, Cultured
  • Humans
  • Immunity, Innate
  • Infections / immunology*
  • Infections / therapy
  • Interleukin-12 / metabolism
  • Interleukin-18 / genetics
  • Interleukin-18 / metabolism
  • Killer Cells, Natural / immunology*
  • Killer Cells, Natural / microbiology
  • Lymph Nodes / immunology*
  • Lymphocyte Activation
  • Lymphocyte Subsets / immunology*
  • Lymphocyte Subsets / microbiology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Precursor Cells, B-Lymphoid / immunology
  • Spleen / immunology*

Substances

  • Interleukin-18
  • Interleukin-12