Dynamic expression of BCL6 in murine conventional dendritic cells during in vivo development and activation.

Ting-Ting Zhang,Samuele Calabro,Giorgio Cattoretti,Dong Liu,Stephanie C Eisenbarth,Ann M Haberman

doi:10.1371/journal.pone.0101208

Ting-Ting Zhang, Samuele Calabro + Show 4 more

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https://doi.org/10.1371/journal.pone.0101208

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Journal: PloS one	Publication Date: Jun 30, 2014
Citations: 10	License type: CC BY 4.0

Affiliation: Yale University, University of Milano-Bicocca

Abstract

The transcriptional repressor BCL6 plays an essential role in the development of germinal center B cells and follicular helper T cells. However, much less is known about the expression and function of BCL6 in other cell types. Here we report that during murine dendritic cell (DC) ontogeny in vivo, BCL6 is not expressed in bone marrow hematopoietic stem cells, common DC precursors and committed precursors of conventional DCs (pre-cDCs), but is elevated in peripheral pre-cDCs. BCL6 protein levels rise as pre-cDCs differentiate into cDCs in secondary lymphoid organs. Elevated protein levels of Bcl6 are observed in all cDC subsets, with CD8α+ cDCs displaying the greatest levels. Co-staining of Ki-67 revealed BCL6hi cDCs to be more proliferative than BCL6lo cDCs. After adjuvant inoculation, BCL6 levels are significantly reduced in the CD11cint MHC class IIhi CD86hi cDCs. Activation-induced BCL6 reduction correlated with reduced proliferation. A LPS injection study further confirmed that, in response to microbial stimuli, BCL6 levels are dynamically regulated during the maturation of CD11cint MHC class IIhi splenic cDCs. This reduction of BCL6 levels in cDCs does not occur after LPS injection in MyD88−/− TRIF−/− mice. Thus, regulation of Bcl6 protein levels is dynamic in murine cDCs during development, maturation and activation in vivo.

Highlights

The transcriptional repressor BCL6 contains a N-terminal BTB/POZ domain and C-terminal zinc finger DNA-binding motifs and represses transcription of a wide range of target proteins and microRNAs
The earliest commitment to the dendritic cell (DC) lineage occurs during the transition from the macrophage and DC precursor (MDP) to the common DC precursor (CDP), which will give rise exclusively to pDCs and pre-conventional DCs (cDCs) [22,23]
We examined BCL6 levels in Lin2 Sca+ Kit+ (LSK) fraction containing hematopoietic stem cells (HSCs), CDPs and pre-cDCs during DC development via flow cytometry

Summary

Introduction

The transcriptional repressor BCL6 contains a N-terminal BTB/POZ domain and C-terminal zinc finger DNA-binding motifs and represses transcription of a wide range of target proteins and microRNAs. The roles of BCL6 in germinal center (GC) B cell development have been extensively studied [3,4,5,6]. Those studies indicate that BCL6 is highly expressed in GC B cells, but subject to multiple layers of regulation, the dysregulation of which can lead to lymphomagenesis [7]. BCL6 is required for the development of T follicular helper T cells (TFH), a helper T cell subset required for the formation of mature and productive GCs [1,8,9]. BCL6 promotes differentiation towards the TFH state by repressing Th1, Th2 or Th17 lineage-specific transcription factors as well as miRNAs that negatively regulate the chemokine receptor CXCR5 [10]

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