IL-4Rα-associated antigen processing by B cells promotes immunity in Nippostrongylus brasiliensis infection
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2013
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PLoS One
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Public Library of Science
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University of Cape Town
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Abstract
In this study, B cell function in protective TH2 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.
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Horsnell, W. G., Darby, M. G., Hoving, J. C., Nieuwenhuizen, N., McSorley, H. J., Ndlovu, H., ... & Dewals, B. (2013). IL-4Rα-associated antigen processing by B cells promotes immunity in Nippostrongylus brasiliensis infection. PLoS pathogens, 9(10), e1003662. doi:10.1371/journal.ppat.1003662