Differential expression of IRF8 in subsets of macrophages and dendritic cells and effects of IRF8 deficiency on splenic B cell and macrophage compartments

IRF8, a transcription factor restricted primarily to hematopoietic cells, is known to influence the differentiation and function of dendritic cells (DC), macrophages, granulocytes and B cells. In human tonsil, IRF8 is expressed at high levels by intrafollicular macrophages and DC, but at much lower levels by tingible body macrophages in germinal centers (GCs) and little, if at all, by follicular DC. Spleens of IRF8-deficient mice had reduced numbers of white pulp follicles and GCs that were irregular in shape. The frequency of follicular B cells was significantly reduced while the population of marginal zone (MZ) B cells was increased. In addition, MZ macrophages were reduced in number and abnormally distributed, while metallophilic macrophages were normal. These findings demonstrate differential requirements for IRF8 among distinct subsets of B cells, DC, and macrophages.