![]() ![]() In contrast to the extensive characterization of lymphoid cells from inflamed RA synovium and synovial fluid, very little is known about B cells present in the joint-draining lymph nodes (or nodes draining other tissues targeted by immune-mediated inflammatory disorders). Results and discussion Rationale and origin of specimens ![]() To specifically address this knowledge gap, here we report the results of analysis of fresh PLNs harvested from discarded tissues from RA patients and patients with other severe lower limb diseases (non-RA), undergoing total knee arthroplasty or lower limb amputation, as well as of cryopreserved cell samples of human reactive and normal lymph nodes (RLNs and NLNs). However, whether specific alterations in resident B-cell subsets, including presence of any Bin-like population, are detectable in human inflamed lymph nodes remains undetermined. ![]() Histological studies of RA LNs are consistent with B-cell follicle hyperplasia and interfollicular invasion 14, and more recent analysis of needle biopsy specimens demonstrated early accumulation of CD19 + cells beginning at the pre-clinical stage 15. Significant evidence also indicates that alterations of draining lymph nodes and lymphatics are associated with human RA including: frequent lymphadenopathy, detection of structural and vascular changes by ultrasound, and rarer complications such as lymphedema and intralymphatic histiocytosis 11- 13. Consistent with this model, despite the non-autoimmune etiology of TNF-tg mice, BCDT in this strain ameliorates disease and restores lymphatic drainage from the affected joints 8- 10. In TNF-tg mice, Bin cells accumulate early in disease development, becoming a predominant fraction as disease progresses when they relocate to the expanded paracortical lymphatic sinusoids, disrupting node histology and likely directly hampering lymphatic flow 6- 8. One such antibody-independent pathogenic mechanism is active in the TNF-tg mouse model of inflammatory-erosive arthritis 5, in which we have shown that B cells, and in particular a unique CD23 +, CD21/35 high, CD1d high subset (Bin cells), contribute to disease exacerbation by compromising lymph node structural integrity and lymphatic drainage function 1, 6, 7. These mechanisms may account for some of the heterogeneity observed in autoimmune patients between clinical efficacy of anti-CD20 B-cell depletion therapy (BCDT), and correlated reduction in titers of different autoantibody types 2- 4. In addition to production of autoantibodies, B cells contribute to the pathogenesis of RA, as well as of other autoimmune/inflammatory diseases, via antibody-independent mechanisms that are still only partially understood 1, 2. Further analyses are necessary to assess the role of CD23 +CD21 hi Bin-like B cells in RA pathogenesis and arthritic flare. Consistent with published mouse data, this population appears to be associated with inflammatory arthritis and distortion of LN architecture. ![]() This is the first description of Bin-like B cells in human inflamed LNs. Histopathology and immunofluorescence analyses were consistent with B follicular hyperplasia and histological alterations in RA vs. Bin-like B cells were shown to be significantly increased in reactive LNs, and strikingly elevated (>30% of total) in RA samples. Here, we report the characterization of resident B-cell populations in fresh popliteal lymph nodes (PLNs) from patients with severe lower limb diseases (non-RA) and rheumatoid arthritis (RA) patients, and from banked, cryopreserved reactive and normal human LN single cell suspension samples. Bin cells contribute to arthritis flare in mice by distorting node architecture and hampering lymphatic flow, but their existence in human inflamed LNs has not yet been described. A unique population of CD23 + CD21 high B cells in inflamed nodes (Bin) has been shown to accumulate in lymph nodes (LNs) draining inflamed joints of TNF-transgenic (TNF-tg) mice. ![]()
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