C1q Production by Bone Marrow Stromal Cells

To the Editor Complement components and their receptors have recently come into focus as key regulators in the clearance of apoptotic cells by human dendritic cells (DC), a subset of phagocytic cells derived from bone marrow stromal cell progenitors [1, 2]. C1q, the first component of the classical pathway of complement activation, is able to bind to the surface of apoptotic cells inducing C3b deposition and promoting the uptake of apoptotic cells by DC via the interaction with C1q receptor and other C1q binding structures (Table 1) [3]. C1q production by human DC has been reported to be restricted to immature DC in vitro, as it is downregulated upon DC maturation [4]. In human bone marrow, active phagocytosis of apoptotic cells and uptake of immune complexes, as well as antigen presentation to lymphocytes, are provided by stromal cells with dendritic morphology that are intermingled with haematopoietic cells. These cells, hereafter referred to as bone marrow stromal DC, contribute to the formation of the bone marrow microenvironment actively participating into the normal haematopoiesis through the constitution of maturational niches [5]. They also have a share in the composition of the bone marrow infiltrates in lymphoid malignancies, although the underlying mechanisms are still unknown [6]. We investigated the expression of C1q in bone marrow stromal cells ex vivo studying 17 bone marrow biopsies with normal histology or non-specific reactive changes by immunohistochemistry and fluorescent in situ hybridization (FISH). By immunohistochemical evaluation, C1q resulted strongly expressed by bone marrow stromal DC (Fig. 1A) and by macrophages (Fig. 1B) in all cases. These results were confirmed by double stainings with CD1a (Fig. 1A, inset) and CD68 (Fig. 1B, inset). FISH for C1q B chain mRNA confirmed that C1q expression in bone marrow stromal cells was due to direct production of C1q and not to C1q uptake (Fig. 1C). Recently, a report by Yamada et al. [7] demonstrated that C1q was able to suppress pro-inflammatory cytokine production (IL12p40, TNF-a) by murine bone marrow-derived DC in vivo. This