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The Journal of Immunology, 2006, 177: 280-289.
Copyright © 2006 by The American Association of Immunologists

Follicular Dendritic Cells Are Related to Bone Marrow Stromal Cell Progenitors and to Myofibroblasts1

Raquel Muñoz-Fernández*, Francisco Javier Blanco*, Cecilia Frecha{dagger}, Francisco Martín{dagger}, Maria Kimatrai*, Ana Clara Abadía-Molina*, José Marcos García-Pacheco{ddagger} and Enrique G. Olivares2,*

* Unidad de Inmunología, Instituto de Biopatología y Medicina Regenerativa, Hospital Universitario "San Cecilio," Universidad de Granada, Granada, Spain; {dagger} Instituto de Parasitología y Biomedicina, Consejo Superior de Investigaciones Científicas, Granada, Spain; and {ddagger} Unidad de Inmunología y Biología Molecular, Hospital do Meixoeiro, Vigo, Spain

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 {alpha}-smooth muscle actin ({alpha}-SM actin) indicated that FDC are closely related to bone marrow stromal cell progenitors. The expression of {alpha}-SM actin also relates FDC with myofibroblasts. Like myofibroblasts, FDC lines expressed stress fibers containing {alpha}-SM actin and were able to contract collagen gels under the effect of TGFbeta1 and platelet-derived growth factor. These findings suggest that FDC are a specialized form of myofibroblast and derive from bone marrow stromal cell progenitors.




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