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Chengrong Yu, Lin Sun, Chang He, Rashid M Mahdi, CHRALES E EGWUAGU; IL-21 induces Expansion of IL-35-producing B cells (i35-Bregs). Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):867.
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IL-35-producing B cells (i35-Bregs) are critical regulators of immunity during autoimmune and infectious diseases and recent studies suggest that IL-35 plus LPS can induce the conversion of naive or IL-10-producing B cells (Bregs) into i35-Breg. Interestingly, while LPS or IL-21 plus CD40 signaling induces naïve B cells to produce IL-10, co-stimulation with LPS plus anti-CD40 inhibits Bregs and promotes i35-Bregs expansion. In this study, we investigated whether similar to IL-35, if IL-21 plus LPS can also induce the expansion of i35-breg population.
CD19+ B cells were isolated by sorting from the spleen of C57BL/6 mice and are activated with LPS or aCD40-/aIgM antibodies in absence or presence of rIL-35 or IL-21. Immunophynotype of the cells was characterized by FACS using labeled mAbs specific to CD19, B220, CD1d, CD5, CD21, CD23, CD27, CD38, CD40, CD138, GL-7, IgM, IgD, IL-10, TNF-a, IL-12p35, EBI3, WSX-1 or IL-12Rb2. The B cells were also characterized by ELISA, PCR and Western blotting.
IL-21 plus CD40 signaling induced IL-10 while IL-21 inhibited LPS-induced IL-10 production. On the other hand, IL-21 plus CD40 or IL-21 plus LPS induced expression of IL-35 (IL-12p35 and Ebi3). Interestingly, co-stimulation of B cells by IL-21 and aCD40/aIgM abs induced more IL-35 compared to stimulation with IL-21 plus LPS.<br />
We show here for the first time that IL-21 induces the expansion of IL-35-producing B cells and suggests that IL-21 and IL-35 may form an axis that promotes the expansion of IL-35+Bregs.<br />
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