Introduction The IL-27 receptor (IL-27R) is expressed on naïve T helper cells. Signaling induces Th1 differentiation and IL-10 production and inhibits Th17 differentiation. In addition, the IL-27R is also expressed on B cells, where it is linked to B cell proliferation and IgG2a class switch recombination. However, its role is not fully understood. We therefore aim to determine the role of IL-27R signalling on B cells, both in T cell independent and in T cell dependent immune responses.
Methods To determine the effect of IL-27 on B cells, we isolated naïve B cells from wild type mice and cultured them in the absence or presence of rIL-27. T cell dependent responses were investigated using the collagen induced arthritis (CIA) model in wild type and IL-27R deficient (WSX-1 deficient) mice. T cell independent B cell responses were investigated using the TNP-Ficoll immunisation model.
Results Naïve wild type B cells cultured in the presence of rIL-27 showed increased proliferation and expression of activation markers. Next, we investigated the role of IL-27R signalling in vivo in CIA. Both the incidence and severity of CIA were significantly lower in IL-27R deficient mice. Splenic germinal centre B cells were decreased in these mice. In addition, both auto-reactive IgM and IgG2a antibody levels were significantly decreased. These data suggest an impairment of B cell immunity in IL-27R deficient mice. However, CIA also depends on T cells. To determine whether the impairment of B cell immunity in IL-27R deficient mice was B cell intrinsic, we used the T cell independent TNP-Ficoll immunisation model. Wild type and IL-27R deficient mice were immunised with TNP-Ficoll i.p. and sacrificed seven days later. IL-27R deficient mice had fewer splenic IgM and IgG3 plasma cells and lower serum TNP specific IgM and IgG3 antibody levels.
Conclusions Here we show that IL-27R signalling on B cells is essential for proliferation and activation of B cells. Impaired B cell immunity in IL-27R deficient mice is caused by an intrinsic B cell defect, leading to impaired plasma cell formation and antibody production in both T cell independent as well as T cell dependent immune responses.