Dynamic Expression of BCL6 in Murine Conventional Dendritic Cells during In Vivo Development and Activation

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 CD8 alpha(+) cDCs displaying the greatest levels. Co-staining of Ki-67 revealed BCL6(hi) cDCs to be more proliferative than BCL6(lo) cDCs. After adjuvant inoculation, BCL6 levels are significantly reduced in the CD11c(int) MHC class IIhi CD86(hi) 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 CD11c(int) 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.