Single-cell profiling (scRNA-seq with paired V(D)J) of the splenic response to VLP immunization in MZB KO versus wild-type mice
The precise role of Marginal Zone B (MZB) cells in shaping the adaptive immune response to virus-like particle (VLP) immunization remains incompletely defined. Here, we combined VLP immunization of wild-type and MZB-deficient mice with single-cell RNA sequencing (scRNA-seq) and paired TCR/BCR profiling of splenocytes. This integrated approach directly links the cellular transcriptome with its unique immune receptor at a single-cell resolution, allowing us to deconvolute the splenic immune landscape and precisely identify the molecular and clonal alterations resulting from the absence of MZB cells.Our analysis provides the first comprehensive insight into the gene expression programs and receptor repertoires that define the disrupted humoral immunity in MZB KO mice following vaccination. This strategy establishes a framework for definitively linking specific immune cell subsets to functional antibody responses and can be broadly applied to dissect the mechanisms of action of other vaccine platforms.