Transmembrane BAFF from rheumatoid synoviocytes requires interleukin‐6 to induce the expression of recombination‐activating gene in B lymphocytes

Rochas, Caroline; Hillion, Sophie; Saraux, Alain; Mageed, Rizgar A.; Youinou, Pierre; Jamin, Christophe; Devauchelle, Valérie

doi:10.1002/art.24498

Cited by 28 publications

(19 citation statements)

References 51 publications

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“…First, we demonstrated that RASF constitutively produce large amount of BAFF and APRIL, expanding recent evidence of overexpression of these factors at mRNA level in RASF 17 18 36. Furthermore, we showed that TLR3 stimulation induced strong and rapid upregulation of BAFF at both mRNA and protein level while APRIL was more modestly modulated and displayed a delayed kinetic of expression, peaking 24–48 h poststimulation.…”

Section: Discussionsupporting

confidence: 74%

A BAFF/APRIL-dependent TLR3-stimulated pathway enhances the capacity of rheumatoid synovial fibroblasts to induce AID expression and Ig class-switching in B cells

Kam²,

et al. 2011

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OBJECTIVES: To dissect the role of toll-like receptor (TLR) signalling and B cell survival/proliferating factors in the crosstalk between rheumatoid arthritis synovial fibroblasts (RASF) and B cells. METHODS: RASF, rheumatoid arthritis dermal fibroblasts (RADF) and osteoarthritis synovial fibroblasts (OASF) were analysed for the expression of B cell survival/proliferating factors BAFF and APRIL in resting conditions and upon stimulation with TLR2/TLR3/TLR4 ligands. Unswitched IgD+ B cells were co-cultured with RASF/OASF/RADF in the presence/absence of TLR ligands and with/without BAFF/APRIL blocking antibodies. Activation-induced cytidine deaminase (AID) mRNA expression, I-C and I-C circular transcripts (CTs; markers of ongoing class-switching to IgG and IgA) and IgM/A/G production were measured to assess functional activation of B cells. RESULTS: TLR3 and to a lesser extent TLR4, but not TLR2 stimulation, induced up to 1000-fold BAFF mRNA and increased soluble BAFF release. APRIL was less significantly regulated by TLR3. Resting and TLR3-stimulated RASF released higher levels of BAFF/APRIL compared with RADF. TLR3 stimulation of RASF but not RADF in co-culture with B cells strongly enhanced AID expression, I-C and I-C CTs and class-switching to IgG/IgA. Blockade of BAFF/APRIL signalling completely inhibited TLR3-induced, RASF-dependent expression of AID, CTs and the secretion of IgG/IgA. CONCLUSIONS: RASF produce high levels of BAFF and APRIL constitutively and in response to TLR3 stimulation. These factors are critical in directly modulating AID expression, class-switch recombination and IgG/IgA production in IgD+ B cells. Overall, this work highlights a novel and fundamental role for the TLR3/B cell survival factor axis in sustaining B cell activation in the rheumatoid arthritis synovium. Conclusions. RASF produce high levels of BAFF and APRIL constitutively and in response to TLR3 stimulation. These factors are critical in directly modulating AID expression, CSR and IgG/IgA production in IgD+ B cells. Overall, we highlight a novel and fundamental role for the TLR3/B cell survival factor axis in sustaining B cell activation in the RA synovium.

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Section: Discussionsupporting

confidence: 74%

A BAFF/APRIL-dependent TLR3-stimulated pathway enhances the capacity of rheumatoid synovial fibroblasts to induce AID expression and Ig class-switching in B cells

Kam²,

et al. 2011

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“…It is interesting that in the RA joint, the accumulated B cells re-express RAG. The data from Rochas et al indicated that 2 separate signals are required for B cells to induce RAG gene expression, the first from transmembrane BAFF on RA FLS and the second from one or more cytokines, including IL-6 [90].…”

Section: Fls Interacts With B and T Cellsmentioning

confidence: 96%

The role of BAFF in the progression of rheumatoid arthritis

2015

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“…There was no difference in BAFF mRNA of FLSs from the synovial tissue of RA patients compared with those from patients with osteoarthritis and the normal controls, but the BAFF mRNA of those cells was enhanced by IFN-γ or TNF-α [82]. In cocultures of peripheral B cells with FLSs from synovial tissue of RA patients, the expression of RAG genes-which could induce a revision of the B-cell receptor genes, resulting in autoreactivity-was induced in peripheral B cells by BAFF and IL-6 [83]. Moreover, a BAFF-dependent class switch recombination was demonstrated in the coculture of peripheral B cells with FLSs from synovial tissue of RA patients [84].…”

Section: Rheumatoid Arthritismentioning

confidence: 96%

The Roles of the TNF-Family Member B-Cell Activation Factor Belonging to the TNF-Family (BAFF) in Autoimmunity

Hirayama¹,

Nagai²

2017

Immunopathogenesis and Immune-Based Therapy for Selected Autoimmune Disorders

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The tumor necrosis factor superfamily (TNFSF) member and cytokine known as B-cell activation factor belonging to the TNF-family (BAFF) has been identified as one of the key factors in the selection and survival of B cells. Overexpression of BAFF in mice leads to autoimmunity, whereas BAFF-deficient mice lack mature B cells. Although under normal concentrations of BAFF, non-self-reactive B cells survived and autoreactive B cells were deleted, a higher concentration of BAFF contributed to the survival of autoreactive B cells and elevated autoantibody production. Lupus-prone mice have increased serum levels of BAFF during the onset and progression of disease. The serum BAFF levels are elevated in patients with autoimmune diseases, such as systemic lupus erythematosus, rheumatoid arthritis, Sjögren's syndrome and ANCA-associated vasculitis, and showed positive correlations with autoantibodies.

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Transmembrane BAFF from rheumatoid synoviocytes requires interleukin‐6 to induce the expression of recombination‐activating gene in B lymphocytes

Cited by 28 publications

References 51 publications

A BAFF/APRIL-dependent TLR3-stimulated pathway enhances the capacity of rheumatoid synovial fibroblasts to induce AID expression and Ig class-switching in B cells

A BAFF/APRIL-dependent TLR3-stimulated pathway enhances the capacity of rheumatoid synovial fibroblasts to induce AID expression and Ig class-switching in B cells

The role of BAFF in the progression of rheumatoid arthritis

The Roles of the TNF-Family Member B-Cell Activation Factor Belonging to the TNF-Family (BAFF) in Autoimmunity

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