Dysregulated B cell function and disease pathogenesis in systemic sclerosis

Abstract

Systemic sclerosis (SSc) is a complex, immune-mediated rheumatic disease characterised by excessive extracellular matrix deposition in the skin and internal organs. B cell infiltration into lesional sites such as the alveolar interstitium and small blood vessels, alongside the production of defined clinically relevant autoantibodies indicates that B cells play a fundamental role in the pathogenesis and development of SSc. This is supported by B cell and fibroblast coculture experiments revealing that B cells directly enhance collagen and extracellular matrix synthesis in fibroblasts. In addition, B cells from SSc patients produce large amounts of profibrotic cytokines such as IL-6 and TGF-β, which interact with other immune and endothelial cells, promoting the profibrotic loop. Furthermore, total B cell counts are increased in SSc patients compared with healthy donors and specific differences can be found in the content of naïve, memory, transitional and regulatory B cell compartments. B cells from SSc patients also show differential expression of activation markers such as CD19 which may shape interactions with other immune mediators such as T follicular helper cells and dendritic cells. The key role of B cells in SSc is further supported by the therapeutic benefit of B cell depletion with rituximab in some patients. It is notable also that B cell signaling is impaired in SSc patients, and this could underpin the failure to induce tolerance in B cells as has been shown in murine models of scleroderma.

Molecular Mechanisms and Risk Factors Related to the Pathogenesis of Peyronie’s Disease

“…B cells contribute to several different fibrotic diseases via a number of mechanisms, including direct cell–cell contact and the production of profibrotic and pro-inflammatory cytokines (e.g., IL-6 and TGF-β1) [ 58 , 59 , 60 ]. Furthermore, decreased IL-10 production by B cells is possibly a factor associated with fibrosis according to previous examinations of systemic sclerosis patients [ 60 , 61 , 62 ]. These studies also showed that increased IL-6 and reduced IL-10 levels in B cells are induced through the activation of the JAK/STAT and TLRs pathways.…”

A preliminary nomogram model for predicting organ damage of patients with diffuse Systemic sclerosis

“…In the early stage of SSc, mast cells, T, B lymphocytes and macrophages in ltrate the diseased tissue and produce cytokines such as IL-6 and TGF-β, which mediate the transdifferentiation of myo broblasts and eventually lead to organ brosis. In this process, IL-6 is in the upstream of the disease [39].Therefore, we speculated that IL-6 may have a better predictive effect in patients with short disease course and in ammation as the main manifestation, while the disease course of our patient was relatively long, and the pathological change of the disease was mainly chronic brosis, serum IL-6 could not well predict the damage of the disease organs.…”

Immunological Profiles in Parry–Romberg Syndrome: A Case–Control Study

“…Several reports have convincingly documented that dysregulated B cell function represents a hallmark of scleroderma diseases. Indeed, B cells have been found in lesional sites such as the alveolar interstitium and small blood vessels, and B lymphocyte subpopulations have been shown to be altered and to display an activated phenotype in scleroderma patients [ 11 , 12 , 13 ]. In our case–control study, B cell subpopulations were very similar in the PRS and CTR patients, except for the unswitched-memory B subset, which was more abundant in the PRS patient.…”