Th17 effector cells support B cell responses outside of germinal centres

PLoS One. 2012;7(11):e49715. doi: 10.1371/journal.pone.0049715. Epub 2012 Nov 16.

Abstract

Th17 cells are pro-inflammatory CD4⁺T cells, which are important in immune responses against fungal pathogens and extracellular bacteria and have also been implicated in various autoimmune syndromes. However, their role in supporting B cell responses in these scenarios remains unclear, representing a significant lapse in our understanding of the role Th17 play in vaccine responses and the regulation of autoimmunity. We employed T cell and B cell receptor transgenic mice specific for model antigens, and adoptive transfer approaches that allowed the tracking of cognate B and T cells in situ and ex vivo using immunological methods. We have found that T cells activated under Th17 polarising conditions have a greater capacity to provide cognate B cell help compared with Th1 polarised populations, supporting higher expansion of antigen specific B cells and enhanced antibody titres. This advantage is associated with the increased persistence of Th17 polarised cells in areas of the lymph nodes where they can provide help (i.e. the B cell follicles). Also the Th17 cells are characterised by their higher expression of ICOS, a costimulatory molecule important for B cell help. Surprisingly, contrary to published reports, Th17 cells were not detected inside germinal centres, although they were found in close proximity to cognate B cells in the follicle early in the genesis of the humoral immune response. These data indicate that, Th17 cells have a more significant role earlier in the initiation/development of the germinal centre response and/or germinal centre-independent events, consistent with their early effector status.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adoptive Transfer
  • Animals
  • B-Lymphocytes / immunology*
  • Cell Communication / immunology*
  • Cell Survival / immunology
  • Germinal Center / immunology*
  • Inducible T-Cell Co-Stimulator Protein / metabolism
  • Lymph Nodes / immunology
  • Mice
  • Th1 Cells / cytology
  • Th1 Cells / immunology
  • Th1 Cells / metabolism
  • Th17 Cells / cytology
  • Th17 Cells / immunology*
  • Th17 Cells / metabolism

Substances

  • Inducible T-Cell Co-Stimulator Protein

Grants and funding

This work was supported by the Oliver Bird Rheumatism Programme. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.