IgE-Fated B Cell Memory Retains Functional Plasticity скачать в хорошем качестве

IgE-Fated B Cell Memory Retains Functional Plasticity

2025 Immcantation Users Group Meeting https://immcantation.github.io/users-... Title: IgE-Fated B Cell Memory Retains Functional Plasticity Speaker: Dr. Kelly Bruton, Stanford University Abstract: Long-lived immunoglobulin (Ig) E responses against innocuous environmental and dietary antigens (Ag) are maintained by an IgG1-dominant memory B cell (MBC) compartment primed for IL-4 responsiveness. The plasticity of the MBC compartment destined for IgE class switch recombination, however, remains poorly understood. In this work, we report a critical IL-4/IL-13 dependency for the pathogenic IgE fate of type 2-polarized MBCs. Initiating a recall response in the absence of IL-4/IL-13 signaling ameliorated the type 2 MBC phenotype in mice and humans and permitted the emergence of long-lived Ag-specific IgG2c+ MBCs. Bulk VDJ sequencing of Ag-specific B cells was performed to investigate how the perturbed recall response modulated the B cell repertoire. Implementing the Immcantation analysis framework, we found that loss of IL-4/IL-13 signaling gave rise to more highly mutated IgG1 and IgG2 clones (SHazaM). Reconstruction of B cell lineage trees (Dowser) revealed that mutated IgG2 B cells were present in trees containing expanded IgM, IgG3, and IgG1 clones, demonstrating that both naïve and class-switched cells can give rise to IgG2. This divergence to a type 1-like response was dependent on IFN-γ signaling and was sustained even beyond therapeutic intervention, revealing fundamental insight into the plasticity of allergen-specific MBCs.