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Search for the precursor of ectopic follicular dendritic cells
Arthritis Res Thervolume 5, Article number: 102 (2003)
Chronic inflammation is often accompanied by the formation of ectopic lymphoid tissue, including infiltrations of T lymphocytes and B lymphocytes, and formation of follicular structures around a network of follicular dendritic cells (FDCs). Ectopic follicular structures may serve as survival niches for undesirable B-cell clones, and FDCs provide powerful survival signals to B lymphocytes . There is broad consensus that FDCs show phenotypic overlap with fibroblasts and are of mesenchymal origin, but the formation of FDCs is poorly understood and a FDC-precursor cell has not been identified . It has been shown in mice that the expression of members of the tumor necrosis factor receptor family, especially of the receptor for lymphotoxin-beta (LTβR), on FDC precursors is a condition for FDC maturation.
This study aims to identify precursor cells for FDCs, and to elucidate the crucial steps that induce FDC networks both under physiological and pathological conditions.
Materials and methods
Fibroblast-like synoviocytes (FLS) derived from synovial biopsies of the knee joint of patients with rheumatoid arthritis (RA) or control arthritides, and fibroblasts from human skin and tonsils were cultured in vitro as described previously . Mesenchymal stem cells (MSC) were cultured from human bone marrow biopsies. The expression of LTβR (as a minimal characteristic of FDC precursors), and of DRC-1 and CD21L (FDC-specific markers) was studied with both immunocytochemical staining (LTβR and DRC-1) and RT-PCR (CD21L).
None of the FLS or fibroblasts expressed LTβR, DRC-1, or CD21L, either spontaneously or after coculture with IFN-γ, IL1-β, tumor necrosis factor alpha, LTα1β2 (gift from Dr Jeff Browning), or combinations thereof. These data suggest that resident tissue fibroblasts or FLS do not contain significant numbers of FDC precursors. In contrast, preliminary experiments with cultured MSC indicate that these cells express the LTβR. Further studies are underway to see whether and under what conditions MSC can be induced to develop the FDC phenotype.
Precursors of FDCs could neither be found in resident tonsillar or dermal fibroblasts, nor in FLS cultured from patients with RA or other types of arthritis. Of interest, in vitro cultured MSC do express the LTβR, and hence fulfill a basic criterion of a putative FDC precursor.
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