Macrophages enhance tumor-derived autophagosomes (DRibbles)-induced B cells activation by TLR4/MyD88 and CD40/CD40L.

Our previous studies have showed that tumor-derived autophagosomes (termed "DRibbles") induce B cell activation, resulting in antibody production and cytokine secretion. Unexpectedly, we found that unfractionated splenocytes produced a higher level of antibody and cytokine than that of purified B cells. In the current study, we investigated the role of accessory cells in DRibbles-induced B cell activation. We found that cognate macrophages, but not T cells, significantly enhanced the B cell activities. Such an enhancement required cell-cell contact. Furthermore, DRibbles stimulation up-regulated CD40L expression on macrophages, resulting in increased level of CD40 expressed on B cells. The accessory role of macrophages in DRibbles-activated B cells is critically dependent on the CD40/CD40L interaction. In addition, the effects of macrophages were found to be largely dependent on TLR4 and MyD88 signaling pathway. Finally, our results showed that macrophages were able to enhance the antigen presentation function of B cells for specific T cell stimulation. Thus, these results suggest that macrophages play an important accessory role for DRibbles-induced B cell immune function.