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Immunology for all: Most scientific communication has historically been limited to visual imagery and the written or spoken word, often in the form of dense articles obscured by jargon. Clear communication of science is vital to enable the public to engage with important scientific discoveries and to limit medical distrust. However, scientific communication is often executed in a way which neglects people with blindness, low vision and diverse needs. Our aim for the exhibit at the Monash Sensory Science Exhibition on Autoimmunity 2023 at Monash University was to develop novel, tactile and informative models to help better communicate the scientific principles that underpin autoimmune disease and immunology. As B‐cell biologists, we decided to focus our exhibit for this workshop on antibody‐mediated autoimmunity. Antibodies are key components of the immune system, providing protection against a range of diverse pathogens. However, in the context of autoimmunity, they can also drive pathology. [ABSTRACT FROM AUTHOR]

Objectives: B cells drive the production of autoreactive antibody‐secreting cells (ASCs) in autoimmune diseases such as Systemic Lupus Erythematosus (SLE) and Sjögren's syndrome, causing long‐term organ damage. Current treatments for antibody‐mediated autoimmune diseases target B cells or broadly suppress the immune system. However, pre‐existing long‐lived ASCs are often refractory to treatment, leaving a reservoir of autoreactive cells that continue to produce antibodies. Therefore, the development of novel treatment methods targeting ASCs is vital to improve patient outcomes. Our objective was to test whether targeting the epigenetic regulator BMI‐1 could deplete ASCs in autoimmune conditions in vivo and in vitro. Methods: Use of a BMI‐1 inhibitor in both mouse and human autoimmune settings was investigated. Lyn−/− mice, a model of SLE, were treated with the BMI‐1 small molecule inhibitor PTC‐028, before assessment of ASCs, serum antibody and immune complexes. To examine human ASC survival, a novel human fibroblast‐based assay was established, and the impact of PTC‐028 on ASCs derived from Sjögren's syndrome patients was evaluated. Results: BMI‐1 inhibition significantly decreased splenic and bone marrow ASCs in Lyn−/− mice. The decline in ASCs was linked to aberrant cell cycle gene expression and led to a significant decrease in serum IgG3, immune complexes and anti‐DNA IgG. PTC‐028 was also efficacious in reducing ex vivo plasma cell survival from both Sjögren's syndrome patients and age‐matched healthy donors. Conclusion: These data provide evidence that inhibiting BMI‐1 can deplete ASC in a variety of contexts and thus BMI‐1 is a viable therapeutic target for antibody‐mediated autoimmune diseases. [ABSTRACT FROM AUTHOR]

Memory B cells (MBCs) are key providers of long-lived immunity against infectious disease, yet in chronic viral infection, they do not produce effective protection. How chronic viral infection disrupts MBC development and whether such changes are reversible remain unknown. Through single-cell (sc)ATAC-seq and scRNA-seq during acute versus chronic lymphocytic choriomeningitis viral infection, we identified a memory subset enriched for interferon (IFN)-stimulated genes (ISGs) during chronic infection that was distinct from the T-bet+ subset normally associated with chronic infection. Blockade of IFNAR-1 early in infection transformed the chromatin landscape of chronic MBCs, decreasing accessibility at ISG-inducing transcription factor binding motifs and inducing phenotypic changes in the dominating MBC subset, with a decrease in the ISG subset and an increase in CD11c+CD80+ cells. However, timing was critical, with MBCs resistant to intervention at 4 weeks post-infection. Together, our research identifies a key mechanism to instruct MBC identity during viral infection. [Display omitted] • scATAC-seq and scRNA-seq reveal expansion of an MBC subset in chronic LCMV infection • A distinct chronic MBC subset is associated with increased IFN-I-associated ISG signature • The chromatin landscape of MBCs is established during a critical window early in infection • IFN-I dynamics govern memory B cell epigenome and phenotype in chronic viral infection Chronic viral infection disrupts the ability to form long-lived B cell-mediated protective immunity, but the mechanisms are unclear. Cooper et al. demonstrate a key role of type I interferon (IFN-I) in governing memory B cell identity and show that the chromatin landscape and phenotype of memory B cells are set during a critical early window of IFN-I exposure. [ABSTRACT FROM AUTHOR]