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bioRxiv · 10.1101/2022.09.18.508441

B cell receptor induced IL-10 production from neonatal CD19+CD43- cells depends on STAT5 mediated IL-6 secretion

Sakai, J.·Yang, J.·Chou, C.-K.·Wu, W.·Akkoyunlu, M.
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Abstract

Newborns are unable to reach the adult-level humoral immune response partly due to the potent immunoregulatory role of IL-10. Increased IL-10 production by neonatal B cells has been attributed to the larger population of IL-10-producting CD43+ B-1 cells in neonates. Here, we show that neonatal CD43- non-B-1 cells also produce substantial amounts of IL-10 following B cell antigen receptor (BCR) activation. In neonatal CD43- non-B-1 cells, BCR engagement activated STAT5 under the control of phosphorylated forms of signaling molecules Syk, Btk, PKC, FAK and Rac1. STAT5 activation led to IL-6 production, which in turn was responsible for IL-10 production in an autocrine/paracrine fashion through the activation of STAT3. In addition to the increased IL-6 production in response to BCR stimulation, elevated expression of IL-6R expression in neonatal B cells rendered them highly susceptible to IL-6 mediated STAT3 phosphorylation and IL-10 production. Finally, IL-10 secreted from neonatal CD43- non-B-1 cells was sufficient to inhibit TNF- secretion by macrophages. Our results unveil a distinct mechanism of IL-6-dependent IL-10 production in BCR-stimulated neonatal CD19+CD43- B cells.

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Sakai, J., Yang, J., Chou, C.-K., Wu, W., Akkoyunlu, M.. 2022-09-18. B cell receptor induced IL-10 production from neonatal CD19+CD43- cells depends on STAT5 mediated IL-6 secretion. https://doi.org/10.1101/2022.09.18.508441

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