The B cell IL-10 receptor suppresses antibody production.

Abstract

Abstract Generation of high affinity, broadly neutralizing antibodies has remained a holy grail in influenza and malaria. Appropriate B cell responses are essential for producing neutralizing antibodies to combat these infections. Additionally, cytokines and their receptors are known to orchestrate the immune response to infections on several levels. However, the regulation of antibody production by cytokine receptors on B cells is not well understood. The anti-inflammatory cytokine, IL-10 activates the JAK-STAT pathway upon binding to the IL-10 receptor (IL-10R), and inhibits production of the pro-inflammatory cytokines. IL-10 is also thought to regulate antibody production but the specific role of IL-10R expressed on B cells is unclear. We hypothesized that the B cell-expressed IL-10R regulates B cell antibody response to infections. To address this, we generated mice with conditional deletion of IL-10R in the B cell lineage. Using these mice, we first examined B cell antibody production in response to LPS and B cell receptor stimulation. Surprisingly, the loss of IL-10R in B cells increased antibody production. Both IgM and IgG antibody secreting cells were significantly increased when the IL-10R was deleted in B cells. Further, higher IL-10 levels were detected in culture supernatants of IL-10R-deficient B cells stimulated with LPS. Our data suggest that the IL-10R on B cells negatively regulates antibody production. Our ongoing experiments are aimed at addressing the molecular basis of this inhibitory influence of the B cell IL-10R on antibody production. This study has implications in the treatment of seasonal infectious diseases such as influenza and malaria, in which a robust antibody response is essential for protective immunity.