Decoding the B-cell immune landscape in duck hepatitis A virus type 3 through single-cell genomics

Antibodies protect the organism against many diseases. How the protective antibody memory response against Duck Viral Hepatitis type 3 (DHAV-3) activates transcriptional programs, cell proliferation, and antigen-specific antibody production is unknown. To explore the mechanisms of DHAV-3 immunity and identify potential therapeutic targets, we performed single-cell RNA sequencing (scRNA-seq) and B cell receptor (BCR) library analyses to characterize the cellular landscape of splenic B-cells from mice immunized with DHAV-3. We observed significant changes in the number and proportion of B cell populations induced by DHAV-3. Through integrating single-cell gene expression profiling and BCR analysis, we have creatively identified a novel IGHV1 germline clone, IGHV1-20, which has not been previously described in the literature. Interestingly, a trend of enhanced cellular communication was observed between a novel B-cell subset, Gm37915+ B cells, and Nuggc+ B cells. Furthermore, we identified two specifically upregulated integrin subunits, ITGAL and ITGB2, in the experimental group (EG), which possibly correlated with the activation status of B cells and enhanced immune-cell interactions. Our findings not only shed light on the immunological characteristics of splenic B cells in the context of DHAV-3 immunity but also provide important advances in our understanding of targeted antibodies against this virus.