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

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 mouse CD43(-) non-B-1 cells also produce substantial amounts of IL-10 following B cell antigen receptor (BCR) activation. In neonatal mouse CD43(-) non-B-1 cells, BCR engagement activated STAT5 under the control of phosphorylated forms of signaling molecules Syk, Btk, PKC, FAK, and Rac1. Neonatal 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 alpha 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 mouse CD43(-) non-B-1 cells was sufficient to inhibit TNF-alpha secretion by macrophages. Our results unveil a distinct mechanism of IL-6-dependent IL-10 production in BCR-stimulated neonatal CD19(+)CD43(-) B cells.

Automated summary

Newborns have a lower humoral immune response than adults due to the immunoregulatory role of IL-10. This study found that both B-1 cells and non-B-1 cells in neonatal mice produce IL-10 in response to B cell antigen receptor (BCR) activation. The production of IL-10 is mediated by the activation of STAT5 and IL-6, and further activates STAT3. IL-10 secreted by neonatal non-B-1 cells can inhibit TNF-alpha secretion by macrophages.