PI3Kg in B cells promotes antibody responses and generation of antibody-secreting cells [scRNA-seq]

The differentiation of naïve and memory B cells into antibody-secreting cells (ASCs) is a key feature of adaptive immunity. The requirement for phosphoinositide 3-kinase delta (PI3Kδ) to support B cell biology has been investigated intensively; however, specific functions of the related phosphoinositide 3-kinase-gamma (PI3Kγ) complex in B-lineage cells have not. Here we report that PI3Kγ promotes robust antibody responses induced by T cell-dependent antigens. The inborn error of immunity caused by human deficiency in PI3Kγ results in broad humoral defects, prompting our investigation of roles for this kinase in antibody responses using mouse models with bulk and single-cell transcriptome as well as B cell receptor repertoire sequencing. For single-cell RNA and B cell receptor sequencing, lymph node cells were analyzed after enrichment for B cell subsets from either wild-type or Pik3cg knockout mice (n = 3 each) immunized three times with NP-Ova emulsified in alum (Day 34). Cells from the different mice were barcoded with mouse TotalSeqTM-C (BioLegend) before mixing and sequencing using two identical lanes.