June 2015
Volume 56, Issue 7
Free
ARVO Annual Meeting Abstract  |   June 2015
IL-21 induces Expansion of IL-35-producing B cells (i35-Bregs)
Author Affiliations & Notes
  • Chengrong Yu
    Laboratory Immunology, National Eye Inst/NIH, Bethesda, MD
  • Lin Sun
    Laboratory Immunology, National Eye Inst/NIH, Bethesda, MD
  • Chang He
    Laboratory Immunology, National Eye Inst/NIH, Bethesda, MD
  • Rashid M Mahdi
    Laboratory Immunology, National Eye Inst/NIH, Bethesda, MD
  • CHRALES E EGWUAGU
    Laboratory Immunology, National Eye Inst/NIH, Bethesda, MD
  • Footnotes
    Commercial Relationships Chengrong Yu, None; Lin Sun, None; Chang He, None; Rashid Mahdi, None; CHRALES E EGWUAGU, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2015, Vol.56, 867. doi:
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    • Get Citation

      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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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: 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.

Methods: 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.

Results: 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 />

Conclusions: 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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