Bone Marrow Dendritic Cell-Mediated Regulation of TLR and B Cell Receptor Signaling in B Cells
Dendritic cells (DCs) play an essential role in regulation of immune responses. In the periphery, Ag presentation by DCs is critical for adaptive responses; for this reason, DCs are often targets of adjuvants that enhance vaccine responses. Activated mature DCs enhance B cell activation and differentiation by providing cytokines like BAFF and a proliferation-inducing ligand. However, the role of immature DCs in B cell tolerance is not well studied. Recently, mouse immature bone marrow-derived DCs (iBMDCs) have been shown to suppress anti-IgM–induced B cell activation. In this study, we tested the ability of mouse DCs to modulate B cell functions during TLR activation. We found that iBMDCs potently suppressed proliferation and differentiation of various B cell subsets on TLR stimulation. However, iBMDCs did not affect CD40-mediated B cell activation. Optimal suppression of B cell activation by iBMDCs required cell contact via the CD22 receptor on B cells. The B cell suppression was a property of iBMDCs or DCs resident in the bone marrow (BM), but not mature BM-derived DCs or DCs resident in the spleen. Presence of iBMDCs also enhanced the Ag-induced apoptotic response of BM B cells, suggesting that the suppressive effects of iBMDCs may have a role in B cell tolerance.
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This work was supported in part by the National Institutes of Health (Grant AI076956 to S.B.; Grants AI56363 and AQI057157 to T.F.T.) and by the Edwards P. Evans Foundation (to S.B.).
Sindhava, Vishal J.; Tuna, Halide; Gachuki, Beth W.; DiLillo, David J.; Avdiushko, Margarita G.; Onami, Thandi M.; Tedder, Thomas F.; Cohen, Don A.; and Bondada, Subbarao, "Bone Marrow Dendritic Cell-Mediated Regulation of TLR and B Cell Receptor Signaling in B Cells" (2012). Microbiology, Immunology, and Molecular Genetics Faculty Publications. 130.