The HMGB1 (C106A) mutation inhibits IL-10-producing CD19(hi)Fc gamma RIIb(hi) B cell expansion by suppressing STAT3 activation in mice

Regulatory B cells have important roles in inflammation and autoimmune diseases. A newly discovered subpopulation of B cells with a CD19(hi)Fc gamma RIIb(hi) phenotype inhibits the proliferation of CD4(+) T cells by secreting interleukin (IL)-10. The expansion of CD19(hi)Fc gamma RIIb(hi) B cells in mouse spleen can be induced by lipopolysaccharide (LPS) or CpG oligodeoxynucleotide stimulation. However, the mechanism of CD19(hi)Fc gamma RIIb(hi) B cell expansion and its role in inflammatory diseases are unclear. Here, we report that, under inflammatory conditions, the proliferation and immunosuppressive function of CD19(hi)Fc gamma RIIb(hi) B cells were decreased in high mobility group box1 (HMGB1) C106A mutant mice, compared with wild-type mice. The HMGB1 (C106A) mutation in B cells reduced STAT3 phosphorylation, restricting the expansion and suppressive function of CD19(hi)Fc gamma RIIb(hi) B cells. Compared with CD19(hi)Fc gamma RIIb(hi) B cells from wild-type mice, CD19(hi)Fc gamma RIIb(hi) B cells from Hmgb1 ((C106A)) mice significantly reduced the survival of mice with sepsis. Recombinant HMGB1 promoted the expansion of IL-10-producing CD19(hi)Fc gamma RIIb(hi) B cells among LPS-activated B cells in vitro. Furthermore, the percentage of CD19(hi)Fc gamma RIIb(hi) regulatory B cells in the peripheral blood was increased in patients with sepsis, compared with healthy controls. These findings implicate the role of HMGB1 in the expansion and immunosuppressive function of CD19(hi)Fc gamma RIIb(hi) B cells.