Second, besides the quantitative aspect discussed in the first point, the function of conventional and inflammatory DCs may be triggered by distinct mechanisms.

Host type I signaling on CD8α+ DCs has been shown to be required for cross-presentation and activation of antitumor CD8+ T cells [41, 42]. It may not, however, be critical for Cetuximab in vitro cross-priming by inflammatory DCs. Third, there is increasing evidence that conventional DCs are critical for tolerance to self. Indeed, targeting an antigen on DCs through the DC-restricted endocytic receptor DEC-205 at the steady state (i.e. in the absence of additional stimuli) provokes a state of tolerance [43] and constitutively DC-depleted mice or mice in which DCs are defective in the uptake of apoptotic cellular antigen develop autoimmunity [44, 45]. These opposing functions of conventional DCs, that is, their capacity to induce either immunity or tolerance, have not been described for inflammatory DCs; thus the two subsets may drive different

responses. Therefore, it seems likely that conventional and inflammatory DCs may play complementary roles in vivo and synergize in the case of infection/inflammation. Conventional DCs appear critical for tolerance to self and for triggering specific immunity, whereas inflammatory DCs are mainly involved in innate defense and in T-cell activation. Whether both cell types synergize for optimal T cell priming in vivo remains to be ioxilan determined. The elucidation of the molecular mechanisms underlying the adjuvant properties of both cell types and their respective Small molecule library order contribution in T-cell activation in vivo is an important issue for optimal vaccine design. We thank Oberdan Leo for careful review and interesting suggestions. The Laboratory of Immunobiology is supported by grants of the Fonds National de la Recherche Scientifique (FNRS)/Télévie, by the Walloon Region (Programme d’excellence CIBLES). C.H. is supported by the Fonds David et Alice Van Buuren. The authors declare no financial or commercial

conflict of interest. “
“Bone morphogenetic proteins (BMPs) are members of the TGF-β superfamily. TGF-β can affect class switch recombination in human B cells, but whether BMPs also play a role have not been tested. We investigated the functional effects of exogenously added BMPs on CD27− naive and CD27+ memory B cells from healthy donors. BMP-2, -4, -6 and -7 inhibited CD40L/IL-21-induced production of IgM, IgG and IgA. BMP-6 reduced Ig production by 70% in memory B cells and more than 55% in naive B cells, whereas the other BMPs were slightly less potent. We observed a striking difference in functional effects between the structurally similar BMP-6 and BMP-7, as BMP-6 mainly inhibited plasmablast differentiation, and BMP-7 mainly induced apoptosis.