Immune complex negatively regulates Toll-like receptor 9-mediated immune responses in B cells through the inhibitory Fc-gamma receptor IIb

Because inappropriate activation of Toll-like receptor9 (TLR9) may induce pathological damage, negative regulation of the TLR9-triggered immune response has attracted considerable attention. Nonpathogenic immune complex (IC) has been demonstrated to have beneficial therapeutic effects in some kinds of autoimmune diseases. However, the role of IC in the regulation of TLR9-triggered immune responses and the underlying mechanisms remain unclear. In this study, it was demonstrated that IC stimulation of B cells not only suppresses CpG-oligodeoxynucleotide (CpG-ODN)-induced pro-inflammatory IL-6 and IgM production, but also attenuates CD40 and CD80 expression. Furthermore, our results suggest that the receptor for the Fc portion of IgG (FcR) IIb is involved in the suppressive effect of IC on TLR9-mediated CD40, CD80 and IL-6 expression. Finally, it was found that IC down-regulates TLR9 expression in CpG-ODN activated B cells. Our results provide an outline of a new pathway for the negative regulation of TLR9-triggered immune responses in B cells via FcRIIb. A new mechanistic explanation of the therapeutic effect of nonpathogenic IC on inflammatory and autoimmune diseases is also provided.