Follicular Dendritic Cells Are Related to Bone Marrow Stromal Cell Progenitors and to Myofibroblasts

Abstract

Follicular dendritic cells (FDC) are involved in the presentation of native Ags to B cells during the secondary immune response. Some authors consider FDC to be hemopoietic cells, whereas others believe them to be mesenchymal cells. The low proportion of FDC in the lymphoid follicle, together with technical difficulties in their isolation, make these cells difficult to study. We show that Fibroblast Medium can be used successfully to isolate and maintain FDC lines. In this culture medium, we obtained 18 FDC lines from human tonsils, which proliferated for as long as 18 wk and showed a stable Ag phenotype as detected by flow cytometry and RT-PCR. FDC lines were CD45-negative and expressed Ags associated to FDC (CD21, CD23, CD35, CD40, CD73, BAFF, ICAM-1, and VCAM-1) and Ags specific for FDC (DRC-1, CNA.42, and HJ2). These cell lines were also able to bind B cells and secrete CXCL13, functional activities characteristic of FDC. Nevertheless, the additional expression of STRO-1, together with CD10, CD13, CD29, CD34, CD63, CD73, CD90, ICAM-1, VCAM-1, HLA-DR, alkaline phosphatase, and α-smooth muscle actin (α-SM actin) indicated that FDC are closely related to bone marrow stromal cell progenitors. The expression of α-SM actin also relates FDC with myofibroblasts. Like myofibroblasts, FDC lines expressed stress fibers containing α-SM actin and were able to contract collagen gels under the effect of TGFβ1 and platelet-derived growth factor. These findings suggest that FDC are a specialized form of myofibroblast and derive from bone marrow stromal cell progenitors.

Follicular dendritic cells: origin, function, and different disease-associated patterns

“…The expression of other fibroblast surface markers, such as ICAM1, VCAM-1, 1B10, and 3C8, on the surface of FDCs has also been reported [3,13,14]. Another study has reported the detection of certain bone marrow stromal progenitor cell-related antigens in a subset of the population in FDC-like cell lines cultured from human tonsils cells, which, along with the identification of some contractile activity within the cells and their expression of α-smooth muscle actin (also expressed in bone marrow stromal cells, adipocytes, and osteoblasts), prompted the authors to conclude a possible origin for the FDCs from a migrating bone marrow mesenchymal cell [15]. Numerous other studies regarding the origin of FDCs have been performed that are beyond the scope of this article, but to date, most scholars believe that FDCs have a nonhematopoietic origin and presumably derive from a migrating mesenchymal cell from the bone marrow.…”

In silico subtraction approach reveals a close lineage relationship between follicular dendritic cells and BP3hi stromal cells isolated from SCID mice

“…As the isolation of intact FDC to homogeneity is not yet technically possible [6,7,11], rather little is currently known about their function and origin.…”

“…To overcome these problems, FDC lines have been established, however, as these cells are maintained over several weeks in culture, their phenotype no longer reflects the in vivo situation [8][9][10][11][12][13]. A number of different approaches for the enrichment and gene expression analysis of FDC have been shown to be more representative of the in vivo situation [6,8,11].…”

“…To overcome these problems, FDC lines have been established, however, as these cells are maintained over several weeks in culture, their phenotype no longer reflects the in vivo situation [8][9][10][11][12][13]. A number of different approaches for the enrichment and gene expression analysis of FDC have been shown to be more representative of the in vivo situation [6,8,11].From a number of experiments, it is apparent that FDC are a highly specialized subset of reticular cells [14][15][16][17][18]. Using BP3, an ectoenzyme of the NAD glycohydrolase family, as a marker antigen for the splenic reticular network of stromal cells, one can distinguish the reticulum cells in the B-cell area from those in the T-cell zone.…”

Pathogenetic and prognostic roles of bloodborne fibrocytes in asthma

“…These cells can exhibit predominant proinflammatory activities or predominant profibrotic properties at tissue sites, depending on the host's response to diverse environmental insults (allergens, viruses, irritants) (Isgrò et al, 2013b) and on the characteristics of the local cell infiltrate and cytokine milieu (Bellini et al, 2012;Sazuka et al, 2014). Similarly to other cells with combined antigenpresenting function and mesenchymal cell-like features (Muñoz-Fernández et al, 2006;Saada et al, 2006), they acquire a myofibroblast-like phenotype in vitro and at the tissue sites because of the expression of adhesion molecules also present on the surface of these cells (Bianchetti et al, 2012b) and the inducible synthesis of the intracellular contractile protein α-smooth muscle actin (α-SMA) (Abe et al, 2001;Schmidt et al, 2003;Mori et al, 2005;Saunders et al, 2009).…”