Production of the plasma-cell survival factor a proliferation-inducing ligand (APRIL) peaks in myeloid precursor cells from human bone marrow

The bone marrow (BM) is an organ extremely efficient in mediating long-term survival of plasma cells (PCs), ensuring an immune humoral memory. This implies that the BM must provide continuously key PC survival factors. Our results show that the BM is an organ constitutively rich in a proliferation-inducing ligand (APRIL), a member of the tumor necrosis factor superfamily implicated in PC survival. APRIL production is induced during hematopoiesis in myeloid cells by non-lineage-committing factors such as stem cell factor, thrombopoietin, IL-3, and FMS-like tyrosine kinase 3 ligand. Notably, APRIL production, both in the human and mouse systems, peaks in myeloid precursor cells, before dropping in fully mature granulocytes. Myeloid cells secrete APRIL that circulates freely in BM plasma to act on PCs, usually at distance from APRIL production sites. Selective APRIL in vivo antagonism and in vitro coculture experiments further demonstrated that myeloid precursor cells mediates PC survival in an APRIL-dependent manner Thus, APRIL production by myeloid precursor cells shows that the 2 main BM functions, hematopoiesis and long-term PC survival, are linked. Such constitutive and high APRIL production may explain why BM mediates long-term PC survival.