Intrinsic lymphotoxin-β receptor requirement for homeostasis of lymphoid tissue dendritic cells

The factors regulating dendritic cell (DC) development and homeostasis are incompletely understood. Here, we demonstrate that DCs express the lymphotoxin (LT)-beta receptor (LT beta R) and that in mice lacking the LT beta R in hematopoietic cells, spleen, and lymph node, CD8(-) DC numbers are reduced. B cells are a key source of LT alpha 1 beta 2 for splenic DC homeostasis, and transgenic overexpression of LT alpha 1 beta 2 on B cells leads to expansion of the CD8- DC compartment. Furthermore, we find that about 5% of splenic DCs are undergoing cell division, and the number of dividing CD8- DCs is disproportionately reduced in the absence of the LT beta R. In parabiosis experiments, splenic DCs were only partially replaced by circulating precursors over a 6 week period. We conclude that LT alpha 1 beta 2 acts on DCs or DC precursors to promote DC homeostasis, and we suggest that DC proliferation is an important pathway for locally maintaining these cells in the steady state.