Systems-level Transcriptomic Analyses for Comprehensive Characterization of the IgG3 B Cell Subclass

Prior studies have suggested that HIV antiviral control may be achieved via the induction of highly polyfunctional IgG3 antibodies (Abs). Here we employ a systems approach to characterize the IgG3 transcriptional profile by identifying intrinsic differences between IgG3 B cells vs IgG1 and IgM B cells that might suggest mechanisms by which B cell molecular circuitry can be programmed to induce and preserve IgG3 Abs. Strikingly, differentially expressed genes between isotype pairs reveal IgG3 is substantially different from other subclasses independent of patent phenotype and time point and subsequently observe clustering by subclass, as opposed to phenotype/time point. Significantly enriched KEGG and Hallmark pathways and GSEA immunological signatures in differentially expressed genes indicate increased activation of basic cellular processes and restriction of transient signaling in IgG3. Therefore this study 1) demonstrates transcriptomic analyses are an effective strategy for characterization of highly homogenous cell subpopulations and 2) offers critical insight into systems level transcriptional signatures of the IgG3 subclass, paving the path for future downstream experiments.