title: IL-4Rα-associated antigen processing by B cells promotes immunity in Nippostrongylus brasiliensis infection.
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.
authors.affiliation: International Centre for Genetic Engineering and Biotechnology (ICGEB) and Institute of Infectious Disease and Molecular Medicine (IIDMM), Division of Immunology, University of Cape Town, Cape Town, South Africa.
authors.forename: William G C
authors.initials: WG
authors.lastname: Horsnell
authors.forename: Matthew G
authors.initials: MG
authors.lastname: Darby
authors.forename: Jennifer C
authors.initials: JC
authors.lastname: Hoving
authors.forename: Natalie
authors.initials: N
authors.lastname: Nieuwenhuizen
authors.forename: Henry J
authors.initials: HJ
authors.lastname: McSorley
authors.forename: Hlumani
authors.initials: H
authors.lastname: Ndlovu
authors.forename: Saeeda
authors.initials: S
authors.lastname: Bobat
authors.forename: Matti
authors.initials: M
authors.lastname: Kimberg
authors.forename: Frank
authors.initials: F
authors.lastname: Kirstein
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Cutler
authors.forename: Benjamin
authors.initials: B
authors.lastname: Dewals
authors.forename: Adam F
authors.initials: AF
authors.lastname: Cunningham
authors.forename: Frank
authors.initials: F
authors.lastname: Brombacher
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D001402:B-Lymphocytes / Q000276:immunology* / Q000473:pathology; D051940:B7-2 Antigen / Q000235:genetics / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology; D007111:Immunity, Cellular; D018793:Interleukin-13 / Q000235:genetics / Q000276:immunology; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics / Q000276:immunology; D009559:Nippostrongylus / Q000276:immunology*; D011956:Receptors, Cell Surface / Q000235:genetics / Q000276:immunology*; D017206:Strongylida Infections / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D018418:Th2 Cells / Q000276:immunology* / Q000473:pathology; D051193:Toll-Like Receptors / Q000235:genetics / Q000276:immunology; D053662:Interleukin-4 Receptor alpha Subunit
chemical_list: D051940:B7-2 Antigen; D000949:Histocompatibility Antigens Class II; D018793:Interleukin-13; D053594:Myeloid Differentiation Factor 88; D011956:Receptors, Cell Surface; D051193:Toll-Like Receptors; C497965:Cd86 protein, mouse; C504002:Il4ra protein, mouse; D053662:Interleukin-4 Receptor alpha Subunit; C507780:Myd88 protein, mouse