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Abstract
IL-27 is a heterodimeric cytokine belonging to the IL-12 family, a family known
to have an important influence on immune responses and the development of
autoimmune diseases. Previous studies in our laboratory have shown that IL-27
plays a critical role in supporting germinal centers (GCs) at least partly through
promoting follicular helper T (TFH) cell function. However, the effects of IL-27
signalling directly on B cells, which also express the IL-27 receptor, are poorly
understood. Here, we aim to investigate the role of IL-27 signalling on B cells in
vivo and in vitro and its contribution to antibody mediated autoimmune disease.
In vitro experiments using mouse and human B cells were performed to
investigate the effects of IL-27 on cytokine production and transcription factor
expression. Although both chains of the IL-27 receptor are expressed by B
cells, its effect on these cells during the antibody response is poorly
characterized. We found that IL-27 stimulation of purified B cells in vitro
enhances expression of the transcription factor Bcl-6 and promotes phenotypic
features of GC B cells. We have also compared Il27ra+/+ and Il27ra-/- B cell
receptor (BCR) transgenic mice (SWHEL) after antigen specific activation using
flow cytometry, serum ELISA and histological analysis. Both Il27ra+/+ and Il27ra-
/- SWHEL B cells form functional GC producing class-switched antibodies. We
then investigated whether IL-27 is critical for the progression of autoimmune
disease mediated by T-dependent B cell responses. Using the Lupus-like
mouse model, Roquinsan/san, we found that Il27ra-/-Roquinsan/san mice have
reduced numbers of GC and ameliorated some aspects of disease in this
model. Thus, we have examined the effects of IL-27 signalling on GC B cell
function, and found IL-27 has a clear proinflammatory effect during antibody
dependent autoimmune responses, and should be considered as a novel
therapeutic target against certain autoimmune diseases, such as lupus.