Deficiency in the transcription factor Bcl6 affects dendritic cell subsets in a broad and distinct manner

Dendritic cells express the transcriptional repressor Bcl6, but its role in the development and function within the dendritic cell (DC) compartment has been heavily debated. Here we show that despite broad changes in phenotype, the cDC1 and cDC2 lineages are generally maintained in mice lacking Bcl6 in DCs. In contrast to intestinal cDC1 and their migratory counterpart in the mesenteric lymph nodes (mLN), spleen and mLN resident cDC1 numbers are maintained in the absence of Bcl6, suggesting local differences regarding the impact of Bcl6 deficiency. Although Bcl6-deficiency caused broad changes in gene expression, cDC1 maintained their ability to cross-present antigen to CD8 T cells. Surprisingly, the absence of Bcl6 in cDC2 caused a complete loss of Notch2-dependent ESAMhi cDC2 in the spleen. Accordingly, DC-targeted Bcl6-deficient mice were unable to mount germinal center responses to blood derived particulate antigen. Our findings establish Bcl6 as an essential transcription factor for a subset of cDC2 and adds to our understanding of the transcriptional landscape underlying cDC2 heterogeneity