IL-4Rα-associated antigen processing by B cells promotes immunity in Nippostrongylus brasiliensis infection

PLoS Pathog. 2013 Oct;9(10):e1003662. doi: 10.1371/journal.ppat.1003662. Epub 2013 Oct 24.

Abstract

In this study, B cell function in protective T(H)2 immunity against N. brasiliensis infection was investigated. Protection against secondary infection depended on IL-4Rα and IL-13; but not IL-4. Protection did not associate with parasite specific antibody responses. Re-infection of B cell-specific IL-4Rα⁻/⁻ mice resulted in increased worm burdens compared to control mice, despite their equivalent capacity to control primary infection. Impaired protection correlated with reduced lymphocyte IL-13 production and B cell MHC class II and CD86 surface expression. Adoptive transfer of in vivo N. brasiliensis primed IL-4Rα expressing B cells into naïve BALB/c mice, but not IL-4Rα or IL-13 deficient B cells, conferred protection against primary N. brasiliensis infection. This protection required MHC class II compatibility on B cells suggesting cognate interactions by B cells with CD4⁺ T cells were important to co-ordinate immunity. Furthermore, the rapid nature of these protective effects by B cells suggested non-BCR mediated mechanisms, such as via Toll Like Receptors, was involved, and this was supported by transfer experiments using antigen pulsed Myd88⁻/⁻ B cells. These data suggest TLR dependent antigen processing by IL-4Rα-responsive B cells producing IL-13 contribute significantly to CD4⁺ T cell-mediated protective immunity against N. brasiliensis infection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigen Presentation*
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / pathology
  • B7-2 Antigen / genetics
  • B7-2 Antigen / immunology
  • Histocompatibility Antigens Class II / genetics
  • Histocompatibility Antigens Class II / immunology
  • Immunity, Cellular*
  • Interleukin-13 / genetics
  • Interleukin-13 / immunology
  • Mice, Inbred BALB C
  • Mice, Knockout
  • Myeloid Differentiation Factor 88 / genetics
  • Myeloid Differentiation Factor 88 / immunology
  • Nippostrongylus / immunology*
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / immunology*
  • Strongylida Infections / genetics
  • Strongylida Infections / immunology*
  • Strongylida Infections / pathology
  • Th2 Cells / immunology*
  • Th2 Cells / pathology
  • Toll-Like Receptors / genetics
  • Toll-Like Receptors / immunology

Substances

  • B7-2 Antigen
  • Cd86 protein, mouse
  • Histocompatibility Antigens Class II
  • Il4ra protein, mouse
  • Interleukin-13
  • Myd88 protein, mouse
  • Myeloid Differentiation Factor 88
  • Receptors, Cell Surface
  • Toll-Like Receptors