TLR7 and CD40 cooperate in IL‐6 production via enhanced JNK and AP‐1 activation

Open Access
Publisher Website
Google Scholar
Abstract
During vaccination or infection, adaptive and innate immune receptors of B cells are engaged by microbial antigens/ligands. A better understanding of how innate and adaptive signaling pathways interact could enlighten B lymphocyte biology as well as aid immunotherapy strategies and vaccine design. To address this goal, we examined the effects of TLR stimulation on BCR and CD40‐induced B cell activation. Synergistic production of IL‐6 was observed in both human and mouse primary B cells stimulated through B cell antigen receptors, CD40 and TLR7, and these two receptors also cooperated independently of BCR signals. The enhanced IL‐6 production was dependent upon the activity of c‐Jun kinase (JNK) and cFos. Dual stimulation through CD40 and TLR7 markedly enhanced JNK activity. The increased level of active JNK in dual‐stimulated cells was accompanied by an increase in the level of active AP‐1 monomers cJun and cFos. The stimulation of B cells through both CD40 and TLR7 therefore enhanced the production of cytokines through increased JNK signaling and AP‐1 activity. In addition, the dual stimulation increased cFos/AP‐1 species in stimulated cells, effectively expanding the repertoire of AP‐1 dimers as compared to singly stimulated B cells.