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 (α-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-γ production in the MLN of C57BL/6 mice receiving α-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-γ and IFN-γinduced 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-γ 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-γ-rich Th1/Th2 settings.

Investigating the importance of B cells and antibodies during Trichuris muris infection using the IgMi mouse

“…All protocols to maintain the parasite and to prepare the E/S were as previously described [ 5 , 13 ]. The concentration of E/S was measured using a Nanodrop 1000 spectrophotometer (Thermo Fisher Science) and aliquoted before storing at − 80 °C.…”

“…To detect T. muris- specific IgG1, IgG2a/c and IgM, an enzyme-linked immunosorbent assay (ELISA) was completed as previously described [ 5 ].…”

“…B cells can mediate protection against pathogens in several different ways: as plasma cells secreting antibody, as antigen-presenting cells (APCs) and as cellular sources of cytokines. We have recently shown that certain mouse strains become more susceptible to T. muris infection in the absence of B cells and antibodies [ 4 , 5 ]. Thus, after α-CD20 monoclonal antibody-mediated B cell depletion, Th2 responses were reduced in the MLN of C57BL/6 mice which consequently were unable to expel the parasite [ 5 ].…”

“…We have recently shown that certain mouse strains become more susceptible to T. muris infection in the absence of B cells and antibodies [ 4 , 5 ]. Thus, after α-CD20 monoclonal antibody-mediated B cell depletion, Th2 responses were reduced in the MLN of C57BL/6 mice which consequently were unable to expel the parasite [ 5 ]. Depletion of B cells using α-CD20 monoclonal antibodies is a useful tool in dissecting out the importance of B cells in infection, but it does not discriminate between the multiple possible roles played by the B cell post infection.…”

Soil-Transmitted Helminth Vaccines: Are We Getting Closer?

“…In mouse models, both antibody-dependent and independent roles for the B cell have been proposed. Using a B-cell depletion strategy in a mouse model, a recent study suggested that the development of a Th2 type immune response to Trichuris infection is dependent on the host's genetic background and is independent of antibodies ( 168 ). Indeed in the context of Trichuris infections, evidence points toward antibody-independent worm expulsion mechanisms ( 169 , 170 ).…”