The Potential Role of Regulatory B Cells in Idiopathic Membranous Nephropathy

Abstract

Regulatory B cells (Breg) are widely regarded as immunomodulatory cells which play an immunosuppressive role. Breg inhibits pathological autoimmune response by secreting interleukin-10 (IL-10), transforming growth factor-β (TGF-β), and adenosine and through other ways to prevent T cells and other immune cells from expanding. Recent studies have shown that different inflammatory environments induce different types of Breg cells, and these different Breg cells have different functions. For example, Br1 cells can secrete IgG4 to block autoantigens. Idiopathic membranous nephropathy (IMN) is an autoimmune disease in which the humoral immune response is dominant and the cellular immune response is impaired. However, only a handful of studies have been done on the role of Bregs in this regard. In this review, we provide a brief overview of the types and functions of Breg found in human body, as well as the abnormal pathological and immunological phenomena in IMN, and propose the hypothesis that Breg is activated in IMN patients and the proportion of Br1 can be increased. Our review aims at highlighting the correlation between Breg and IMN and proposes potential mechanisms, which can provide a new direction for the discovery of the pathogenesis of IMN, thus providing a new strategy for the prevention and early treatment of IMN.

Exploring the Differences in Molecular Mechanisms and Key Biomarkers Between Membranous Nephropathy and Lupus Nephritis Using Integrated Bioinformatics Analysis

“…IFN-α binds cell surface receptors and induces antiviral activity in a variety type of cells (Barchet et al, 2005;Agrawal and Gupta, 2011). IFN-α also activates regulatory B cells (Breg) (Menon et al, 2016;Dong et al, 2020). IFN-β is produced FIGURE 3 | Detailed information related to changes in the biological function of DEGs was provided in the dataset by enrichment analysis.…”

“…IFN-α binds cell surface receptors and induces antiviral activity in a variety type of cells ( Barchet et al, 2005 ; Agrawal and Gupta, 2011 ). IFN-α also activates regulatory B cells (Breg) ( Menon et al, 2016 ; Dong et al, 2020 ). IFN-β is produced in large quantities by fibroblasts ( Gao et al, 2021 ).…”

B Cells in Primary Membranous Nephropathy: Escape from Immune Tolerance and Implications for Patient Management

“…Meanwhile, there is conflicting evidence regarding the expression of Bregs, which usually regulate and suppress memory B cell development arising from T FH -B cell interactions, in the context of MN. Whereas some studies have suggested Bregs were decreased in patients with MN, and the population rose with successful treatment of MN, others showed higher concentrations of Bregs compared to healthy controls and patients with nonimmune causes of chronic kidney disease, though this may be a compensatory response rather than disease-causing per se [99,[110][111][112]. It is crucial to note that Bregs are composed of various B cell subpopulations, including CD19 + CD5 + CD1d hi cells that secrete IL-10, CD19 + CD5 + GzmB + cells that secrete granzyme B, as well as other classes of B cells, and that the limited studies looking at Bregs in MN have focused primarily on IL-10-secreting Bregs.…”

Helper T Cells in Idiopathic Membranous Nephropathy

“…They can also secrete IL-10, but it does not suffice to block the development of the immune response. It was further speculated that the elevated Breg subsets were Br1 cells ( 119 ). As mentioned above, there is an antagonistic relationship between Treg and Th17 cells in terms of differentiation, function and other aspects, and imbalance of Th17/Treg has been observed in many autoimmune diseases.…”