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*
Department of Cell Biology and Histology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands;
Department of Pathology, Slotervaart Hospital, Amsterdam, The Netherlands; and
Jan van Breemen Institute for Rheumatology, Amsterdam, The Netherlands
The production of IgG rheumatoid factors in the inflamed synovium
of many patients with rheumatoid arthritis (RA) implies that local
sites exist where plasma cell precursors undergo isotype switching and
affinity maturation by somatic mutation and selection. Lymphonodular
infiltrates of the synovium-containing germinal centers (GCs), are
candidates to fulfill such function in the rheumatoid patient. It has
been suggested that these GCs are organized around, obviously ectopic,
follicular dendritic cells (FDCs). The present study attempts to find
out whether these putative FDCs 1) are specific for RA, 2) have the
same phenotype and functional capacity as FDCs in lymphoid organs, and
3) may locally differentiate from fibroblast-like synoviocytes (FLS).
Synovial biopsies from patients with RA versus non-RA, yet arthritic
backgrounds, were compared. Cells with the FDC phenotype were found in
both RA and non-RA tissues as well as in single cell suspensions
thereof. When FLS were cultured in vitro, part of these cell lines
could be induced with IL-1ß and TNF-
to express the FDC phenotype,
irrespective of their RA or non-RA background. By contrast, the FDC
function, i.e., stable binding of GC B cells and switching off the
apoptotic machinery in B cells, appeared to be the prerogative of
RA-derived FLS only. The present data indicate that FDC function of FLS
in RA patients is intrinsic and support the idea that synovial
fibroblast-like cells have undergone some differentiation process that
is unique for this disease.
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