The essential role played by B cells in supporting protective immunity againstTrichuris murisinfection is dependent on host genetic background and is independent of antibody

Abstract

AbstractThis study investigates the role of B cells in immunity toTrichuris muris(T. muris) infection in two genetically distinct strains of mouse, using anti-CD20 monoclonal antibody (mAb) (Genentech-clone 5D2) to deplete B cells. Data is presented for the mouse strains: C57BL/6 and BALB/c, which mount mixed Th1/Th2, and highly polarised Th2 immune responses toT. muris, respectively. C57BL/6 mice receiving anti-CD20 treatment prior to and during, or anti-CD20 treatment that commenced two weeks post infection (p.i.), were susceptible toT. muris. Parasite-specific IgG1 antibodies were absent and Th2 type cytokines produced by mesenteric lymph nodes cells from mice receiving α-CD20 mAb treatment were significantly lower than produced by cells from isotype control treated mice. T follicular helper cells were also significantly reduced. Importantly, and in complete contrast, BALB/c mice were still able to expelT.murisin the absence of B cells, revealing that the essential role played by B cells in protective immunity was dependent on genetic background. To explore whether the important role played by the B cell in the protective immune response of C57BL/6 mice was in enabling strong Th2 responses in the presence of IFN-γ, IFN-γ was blocked using anti-IFN-γ mAb post B cell depletion. Depleting IFN-γ, in the absence of B cells restored worm expulsion in the absence of parasite-specific IgG1/IgG2c and partially rescued theT. murisspecific IL-13 response. Thus, our data suggest an important, antibody independent role for B cells in supporting Th2 type immune responses in mixed IFN-γ-rich Th1/Th2 immune response settings.Author summaryHow B cells contribute to protective immunity against parasitic nematodes remains unclear, with their importance as accessory cells under-explored. This study reveals that, on some genetic backgrounds, B cells are important for the expulsion ofT. murisby acting as accessory cells, supporting Th2 immune responses.