B cells regulate CD4+ T cell responses to papain following B cell receptor-independent papain uptake

J Immunol. 2014 Jul 15;193(2):529-39. doi: 10.4049/jimmunol.1303247. Epub 2014 Jun 13.

Abstract

Papain, a cysteine protease allergen with inherent adjuvant activity, induces potent IL-4 expression by T cells in the popliteal lymph nodes of mice following footpad immunization. In this study, we identify a novel, non-BCR-mediated capacity for B cells to rapidly bind and internalize papain. B cells subsequently regulate the adaptive immune response by enhancing ICOS expression on CD4(+) T cells and amplifying Th2 and follicular helper T cell induction. Ab blockade of ICOS ligand, expressed by popliteal lymph node B cells, but not dendritic cells, at the peak of the response inhibits IL-4 responses in wild-type mice but not B cell-deficient mice. Thus, B cells play a critical role in amplifying adjuvant-dependent Th2 polarization following noncanonical acquisition and internalization of the cysteine protease papain.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / metabolism
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / metabolism
  • Cells, Cultured
  • Flow Cytometry
  • Immunization / methods
  • Inducible T-Cell Co-Stimulator Protein / immunology
  • Inducible T-Cell Co-Stimulator Protein / metabolism
  • Interleukin-4 / immunology
  • Interleukin-4 / metabolism
  • Lymph Nodes / cytology
  • Lymph Nodes / immunology
  • Lymph Nodes / metabolism
  • Mice
  • Mice, 129 Strain
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Microscopy, Confocal
  • Microscopy, Fluorescence, Multiphoton
  • Papain / administration & dosage
  • Papain / immunology*
  • Papain / metabolism
  • Protein Binding / immunology
  • Receptors, Antigen, B-Cell / immunology*
  • Receptors, Antigen, B-Cell / metabolism
  • Th2 Cells / immunology
  • Th2 Cells / metabolism

Substances

  • Icos protein, mouse
  • Inducible T-Cell Co-Stimulator Protein
  • Receptors, Antigen, B-Cell
  • Interleukin-4
  • Papain