Abstract
Bregs (regulatory B cells) are important in immune regulation. The regulatory factors on Breg functions are less understood. IGF2 (Insulin-like growth factor 2) is capable of inducing hematopoietic stem cell differentiation. This study aims to investigate the role of IGF2 in the development of Bregs and enhancement of Breg’s function. In this study, the expression of IGF1R and IGF2R in OVAsBCs (ovalbumin (OVA)-specific B cells) was assessed by real time RT-PCR and Western blotting. The releasing of interleukin (IL)-10 from OVAsBCs and OVAsBC proliferation were assessed by enzymelinked immunoassay and proliferation assay. The role of IGF2 in enhancing OVAsBCs’ function was tested with an intestinal allergic inflammation mouse model. The results showed that OVAsBCs
expressed high levels of IGF2R (IGF2 receptor). Exposure to both IGF2 and specific Ag (antigen), OVA, markedly
enhanced the expression of IL-10 in OVAsBCs, as well as enhanced the IL-10⁺ OVAsBC proliferation. The concurrent exposure to IGF2 and specific Ag markedly induced the IL-10 promoter DNA demethylation via activating the STAT5 pathway. IGF2 also enhanced the OVAsBC proliferation in vivo and enhanced the effect of Ag-specific immunotherapy on inhibiting allergic inflammation in the intestine. We conclude that OVAsBCs express high levels of IGF2R. IGF2
increases the expression of IL-10 in OVAsBCs, enhances OVAsBC proliferation and the inhibitory effect on allergic
inflammation.