Bone marrow dendritic cell-mediated regulation of TLR and B cell receptor signaling in B cells

Vishal J. Sindhava, Halide Tuna, Beth W. Gachuki, David J. DiLillo, Margarita G. Avdiushko, Thandi M. Onami, Thomas F. Tedder, Donald A. Cohen, Subbarao Bondada

Research output: Contribution to journalArticlepeer-review

13 Scopus citations


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.

Original languageEnglish
Pages (from-to)3355-3367
Number of pages13
JournalJournal of Immunology
Issue number7
StatePublished - Oct 1 2012

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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