2017.12.29 Viewing immunological trajectories of B cells through the lens of molecular circuits and cellular motility
报告人：徐和平, PhD, Postdoctoral Associate, Broad Institute
Effective antibody protections against infection or in response to vaccination require productive T cell-dependent B cell immune responses. Upon recognition of antigen, B cells undertake a bifurcated response in which some cells rapidly differentiate into plasmablasts while others migrate to germinal center (GC) area, where activated B cells diversify their immunoglobulin (Ig) genes by somatic hypermutation (SHM) while undergoing clonal expansion and positive selection. This selection process enables the generation of clones expressing higher affinity antigen-receptors that are eventually secreted as antibodies. Our works identified a double-negative feedback loop between the transcription factors IRF4 and IRF8 which initiate the bifurcation of B cell developmental trajectories. Intravitial imaging studies demonstrated that T–B-cell entanglement and ICOSL-driven feed-forward as critical cellular mechanisms supporting germinal center selection. By coupling the analysis of IgH variable sequences with genomic states using scRNA-seq data, we revealed that higher affinity GC B cells express a distinctive mitotic gene module and undergo more rapid cell division that promote positive selection.