The Essential Role Played by B Cells in Supporting Protective Immunity Against Trichuris muris Infection Is by Controlling the Th1/Th2 Balance in the Mesenteric Lymph Nodes and Depends on Host Genetic Background.

Abstract

How B cells contribute to protective immunity against parasitic nematodes remains unclear, with their importance as accessory cells underexplored. In this study, anti-CD20 monoclonal antibody (alpha-CD20 mAb)-mediated depletion of B cells from C57BL/6 mice revealed an important role for B cells in supporting Th2 immune responses and thus expulsion of Trichuris muris (T. muris). C57BL/6 mice normally mount mixed Th1/Th2 immune responses to T. muris and expel the parasite by the third week post infection. However, B cell-depleted C57BL/6 had significantly reduced Th2-type cytokines post infection and failed to expel the parasite. IFN- gamma production in the MLN of C57BL/6 mice receiving alpha-CD20 mAb treatment was not affected, collectively resulting in an overall change in Th1/Th2 balance in favor of Th1. Further, the expression of IFN-gamma and IFN-gamma-induced genes at the effector site, the gut, was significantly increased in the absence of B cells. Interestingly, and in complete contrast, BALB/c mice, which mount strongly polarized Th2 immune responses, rather than mixed Th1/Th2 immune responses, were still able to expel T. muris in the absence of B cells. We thus hypothesized that the B cell plays a critical role in enabling strong Th2 responses in the context of mixed Th1/Th2 settings, with the role becoming redundant in highly Th2 polarized environments. In support of this, neutralization of IFN-gamma in B cell depleted C57BL/6 restored resistance against T. muris infection. Thus, our data suggest an important role of B cells in supporting Th2-type immune responses in mixed IFN-gamma-rich Th1/Th2 settings.

Publication
Front Immunol