A nonredundant role for IL-21 receptor signaling in plasma cell differentiation and protective type 2 immunity against gastrointestinal helminth infection

J Immunol. 2010 Nov 15;185(10):6138-45. doi: 10.4049/jimmunol.1001703. Epub 2010 Oct 6.

Abstract

Pathogen-specific Ab production following infection with the gut-dwelling roundworm Heligmosomoides polygyrus is critical for protective immunity against reinfection. However, the factors required for productive T cell-B cell interactions in the context of a type 2-dominated immune response are not well defined. In the present study, we identify IL-21R signaling as a critical factor in driving pathogen-specific plasma cell differentiation and protective immunity against H. polygyrus in mice. We show that B cells require direct IL-21R signals to differentiate into CD138(+) plasma cells. In contrast, IL-21R signaling is dispensable for germinal center formation, isotype class switching, and Th2 and T follicular helper cell differentiation. Our studies demonstrate a selective role for IL-21 in plasma cell differentiation in the context of protective antiparasitic type 2 immunity.

Publication types

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

MeSH terms

  • Animals
  • Cell Differentiation / immunology*
  • Cell Separation
  • Cytokines / biosynthesis
  • Cytokines / immunology
  • Enzyme-Linked Immunosorbent Assay
  • Flow Cytometry
  • Immunohistochemistry
  • Interleukin-21
  • Interleukins / immunology
  • Interleukins / metabolism
  • Intestinal Diseases, Parasitic / immunology*
  • Intestinal Diseases, Parasitic / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Nematospiroides dubius / immunology
  • Plasma Cells / cytology*
  • Plasma Cells / metabolism
  • Receptors, Interleukin-21 / immunology*
  • Receptors, Interleukin-21 / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction / immunology
  • Strongylida Infections / immunology*
  • Strongylida Infections / metabolism
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism

Substances

  • Cytokines
  • Interleukins
  • Receptors, Interleukin-21
  • Interleukin-21