Bone Marrow Dendritic Cell-Mediated Regulation of TLR and B Cell Receptor Signaling in B Cells

Authors

Vishal J. Sindhava, University of Pennsylvania
Halide Tuna, University of KentuckyFollow
Beth W. Gachuki, University of KentuckyFollow
David J. DiLillo, Duke University
Margarita G. Avdiushko, University of KentuckyFollow
Thandi M. Onami, University of Tennessee - Knoxville
Thomas F. Tedder, Duke University
Don A. Cohen, University of KentuckyFollow
Subbarao Bondada, University of KentuckyFollow

Abstract

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.

Document Type

Article

Publication Date

10-1-2012

Notes/Citation Information

Published in The Journal of Immunology, v. 189, issue 7, p. 3355-3367.

Copyright © 2012 by The American Association of Immunologists, Inc.

Digital Object Identifier (DOI)

https://doi.org/10.4049/jimmunol.1101352

Funding Information

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.).

Repository Citation

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.
https://uknowledge.uky.edu/microbio_facpub/130