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Biology of B cell LgD low (BDL) and their cellular target CD4+Foxp3+ T regulatory cells

Applicant Dr. Zivar Hajiyeva
Subject Area Molecular and Cellular Neurology and Neuropathology
Term from 2022 to 2024
Project identifier Deutsche Forschungsgemeinschaft (DFG) - Project number 498199061
 
Final Report Year 2024

Final Report Abstract

Multiple sclerosis (MS) is the most common autoimmune disorder affecting the central nervous system (CNS). This disease causes significant damage to both myelin and axons within the CNS. Research has used experimental autoimmune encephalomyelitis (EAE), a mouse model of MS, to better understand this disorder's mechanisms. In these experiments, mice deficient in B cells (μMT) did not recover from EAE symptoms. This deficiency was linked to a substantial reduction in the population of Foxp3+CD4+ T regulatory cells (Treg) in the spleen. Treg cells play a crucial role in maintaining immune tolerance and preventing autoimmune responses. A novel subset of regulatory B cells, termed B cell IgD Low (BDL), has been shown to interact with Treg cells, inducing their proliferation and maintaining their numbers at levels necessary for recovery from EAE. This interaction suggests that BDL cells are essential for regulating and maintaining immune balance. However, BDL is a rare population of B cells, making it difficult to understand their biology and potential clinical applications. The goal of our current study was to create conditions that would facilitate BDL expansion and proliferation while maintaining their phenotypic and functional stability. Using a modified 40LB feeder cell line, BDL were expanded up to 60-fold from various mouse backgrounds while maintaining their phenotype and function. Cryopreserved BDL also retained their regulatory capabilities. The findings suggest that the 40LB culture system can reliably expand and store BDL, which could have therapeutic applications in autoimmune diseases. Future work will further explore the mechanisms of BDL-induced Treg proliferation and potential clinical applications.

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