Biology subjects

Blanfeld, M.

Publications and source records attributed to Blanfeld, M..

3 recordsLinked to original sources

bioRxiv2026

Targeting soluble immunoglobulins ameliorates idiopathic multicentric Castleman disease in a mouse model

Idiopathic multicentric Castleman disease (iMCD) is a rare lymphoproliferative disorder that affects lymph nodes at multiple sites and can progress to life-threatening organ dysfunction. While curative therapies remain unavailable, largely due to a critical gap in understanding the diseases underlying etiology, the cytokine interleukin-6 (IL-6) is recognized as a major pathogenic driver, particularly in iMCD patients with plasmacytic lymphadenopathy. Here, we demonstrate the presence of Foxp3-expressing cells alongside plasma cells within germinal centers of lymph nodes from such iMCD patients. Based on this observation, we directed IL-6 overexpression specifically to Foxp3+ Treg cells and established a novel preclinical mouse model of iMCD. This targeted approach successfully recapitulated the key characteristics of iMCD in mice, including multifocal lymphadenopathy, splenomegaly, anemia, thrombocytopenia, marked plasmacytosis, and mortality in young adults. Advanced disease was characterized by renal pathology, including proteinuria and elevated creatinine levels. In this model, IL-6 directly promoted plasmacytosis, resulting in profound IgG1 hyperimmunoglobulinemia. Genetic ablation of soluble immunoglobulin production ameliorated iMCD symptoms, prevented renal dysfunction, and significantly extended survival. Our findings identify IL-6-driven IgG1 plasmacytosis as a critical pathogenic factor in iMCD, shedding light on the mechanisms underlying its development. Key pointsO_LITransgenic IL-6 expression in Foxp3+ cells models iMCD in mice and drives lethal IgG1 plasmacytosis C_LIO_LILoss of soluble immunoglobulins prevented renal impairment and prolonged survival in iMCD-like mice C_LI

immunology↗

bioRxiv2025

B cells maintain the homeostasis of splenic marginal zone antigen-presenting cells to promote the anti-viral CD8+ T cell response

Natural killer and CD8+ T cells are critical in the elimination of blood-borne viruses such as cytomegalovirus (CMV); however, the role of B cells in this process is less clear. Here, using the murine CMV (MCMV) infection model, we demonstrated that the B cell-deficient mice mounted a weaker primary virus-specific CD8+ T cell response than their wild-type counterparts, which was associated with increased viral transcription. Notably, we found that the contribution of B cells to the CD8+ T-cell-mediated anti-viral response was not associated with their ability to generate antibodies but with their ability to sustain Langerin+ type 1 conventional dendritic cells (cDC1s), a dendritic cells (DC) subset known for being involved in viral and bacterial clearance in the marginal zone of the spleen. Furthermore, we found that the presence of Langerin+ cDC1s is dependent on B cells expressing lymphotoxin (LT{beta}) to maintain CD169+ marginal metallophilic macrophages (MMMs). We further discovered, using ligand-receptor interaction analyses, that the communication between MMMs and Langerin+ cDC1s was mediated via VCAM1 - ITGA4/ITGB1 interaction. Thus, our data reveals that B cell regulate the development of MMMs in the spleen via LT{beta} expression and consequently sustain Langerin+ cDC1s homeostasis for effective initiation of an anti-viral CD8+ T cell response. Overall, our study offers a new perspective on how B cells maintain the homeostasis of antigen-presenting cells in the splenic marginal zone and thus indirectly affect the virus-specific CD8+ T cell response, which could potentially be extended to other infectious and autoimmune diseases as well as tumors.

immunology↗

bioRxiv2023

Embryo-restricted responses to maternal IL-17A promote neurodevelopmental disorders in mouse offspring

Prenatal imprinting to interleukin 17A (IL-17A) triggers behavioral disorders in offspring. However, reported models of maternal immune activation utilizing immunostimulants, lack specificity to elucidate the anatomical compartments of IL-17As action and the distinct behavioral disturbances it causes. By combining transgenic IL-17A overexpression with maternal deficiency in its receptor, we established a novel model of prenatal imprinting to maternal IL-17A (acronym: PRIMA-17 model). This model allowed us to study prenatal imprinting established exclusively through embryo-restricted IL-17A responses. We demonstrated IL-17A transfer across the placental barrier and subsequent development of selected behavioral deficits in mouse offspring. More specifically, embryonic responses to IL-17A resulted in communicative impairment in early-life measured by reduced numbers of nest retrieval calls. In adulthood, IL-17A-imprinted offspring displayed an increase in anxiety-like behavior. We advocate our PRIMA-17 model as a useful tool to study neurological deficits in mice.

neuroscience↗