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

• Main Authors: William G C Horsnell, Matthew G Darby, Jennifer C Hoving, Natalie Nieuwenhuizen, Henry J McSorley, Hlumani Ndlovu, Saeeda Bobat, Matti Kimberg, Frank Kirstein, Anthony J Cutler, Benjamin Dewals, Adam F Cunningham, Frank Brombacher
• Format: Article
• Language: English
• Published: Public Library of Science (PLoS) 2013-10-01
• Series: PLoS Pathogens
• Online Access: https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24204255/pdf/?tool=EBI
• ISSN: 1553-7366; 1553-7374

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.