Helicobacter infection is a key cause of gastric B cell mucosa-associated lymphoid tissue (MALT) lymphoma. This study examined the role of B cell-activating factor (BAFF), a major driver of B cell proliferation and many B cell disorders, in this malignancy using a model in which conditional knockout mice for NOD-like receptor family CARD domain-containing 5 (Nlrc5) are infected with Helicobacter felis. Gastric BAFF production was significantly increased in H. felis-infected Nlrc5 mice compared to wild-type. Blocking BAFF signalling, before or after the onset of Helicobacter-induced gastritis, significantly reduced MALT development, with fewer gastric B cell follicles and reduced gland hyperplasia. BAFF blockade also reshaped the immune cell landscape in the stomach, resulting in fewer CD4 T cells, Tregs, macrophages and dendritic cells. Using a cell culture model, we identified the protein-coding BAFF transcripts that are upregulated in NLRC5-deficient macrophages stimulated with either H. felis or the NLRC5 agonist, lipopolysaccharide. Among the upregulated variants, TNFSF13B (BAFF)-206 acts as a transcription factor and is reported to enhance BAFF production in autoimmune diseases and cancer. Altogether, these findings implicate the NLRC5-BAFF signalling axis in Helicobacter-induced B cell MALT lymphoma, highlighting BAFF inhibition as a potential therapeutic approach.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.1002/eji.202451355 | DOI Listing |
Eur J Immunol
December 2024
Centre for Innate Immunity and Infectious Diseases, Hudson Institute of Medical Research, Clayton, Victoria, Australia.
Helicobacter infection is a key cause of gastric B cell mucosa-associated lymphoid tissue (MALT) lymphoma. This study examined the role of B cell-activating factor (BAFF), a major driver of B cell proliferation and many B cell disorders, in this malignancy using a model in which conditional knockout mice for NOD-like receptor family CARD domain-containing 5 (Nlrc5) are infected with Helicobacter felis. Gastric BAFF production was significantly increased in H.
View Article and Find Full Text PDFInt J Mol Sci
November 2024
University Hospital St. Ivan Rilski, Laboratory of Clinical Immunology, Department of Clinical Immunology, Medical Faculty, Medical University of Sofia, 15 Akademik Iv. E. Geshov Blvd., 1431 Sofia, Bulgaria.
Autoimmune diseases represent a severe personal and healthcare problem that seeks novel therapeutic solutions. Mesenchymal stem cells (MSCs) are multipotent cells with interesting cell biology and promising therapeutic potential. The immunoregulatory effects of secretory factors produced by umbilical cord mesenchymal stem cells (UC-MSCs) were assessed on B lymphocytes from 17 patients with systemic lupus erythematosus (SLE), as defined by the 2019 European Alliance of Associations for Rheumatology (EULAR)/American College of Rheumatology (ACR) classification criteria for SLE, and 10 healthy volunteers (HVs).
View Article and Find Full Text PDFBioDrugs
December 2024
Department of Allergy and Clinical Immunology, St James' University Hospital, Leeds, UK.
B-cell depleting therapy (BCDT) has revolutionised the treatment of B-cell malignancies and autoimmune diseases by targeting specific B-cell surface antigens, receptors, ligands, and signalling pathways. This narrative review explores the mechanisms, applications, and complications of BCDT, focusing on the therapeutic advancements since the introduction of rituximab in 1997. Various monoclonal antibodies and kinase inhibitors are examined for their roles in depleting B cells through antibody-dependent and independent mechanisms.
View Article and Find Full Text PDFClin Rheumatol
December 2024
Department of Rheumatology and Immunology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Lujiang Str 17, Hefei, 230001, Anhui, China.
Objective: To examine the effectiveness and safety of two different B cell activating factor/proliferation-inducing ligand inhibitors, telitacicept and belimumab, in treating patients with active systemic lupus erythematosus (SLE).
Methods: Patients with active SLE who received belimumab (n = 100) or telitacicept (n = 101) from 2019 to 2023 at multiple centers in China were retrospectively collected, and the effectiveness and safety of telitacicept and belimumab was evaluated. The subgroups of lupus nephritis and hematologic abnormalities were analyzed to explore if there were any differences in the efficacy of the two biologics on improving kidney and blood systems.
J Inflamm Res
December 2024
Aier Academy of Ophthalmology, Central South University, Changsha, People's Republic of China.
Purpose: In this study, we aimed to investigate the relationship between the intraocular levels of inflammatory factors and myopia-related retinal vascular and neuronal degeneration.
Patients And Methods: One hundred and forty-seven patients with Implantable Collamer Lens (ICL) implantation were enrolled and all participants received comprehensive ophthalmic examination. About 100~150 ul of aqueous humor was collected immediately before ICL surgery.
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!