Programming Isotype-Specific Plasma Cell Function

Helper T cell induced plasma cells (PCs) that secrete class-switched neutralizing antibody are paramount to effective immunity. Following class-switch recombination (CSR), antigen-activated B cells differentiate into extrafollicular PCs or mature in germinal centers (GCs) to produce high-affinity memory B cells and follicular PCs. Many studies focus on the core transcriptional programs that drive central PC functions of longevity and antibody secretion. However, it is becoming clear that these central programs are further subdivided across antibody isotype with separable transcriptional trajectories. Divergent functions emerge at CSR, persist through PC terminal differentiation and further assort memory PC function following antigen recall. Here, we emphasize recent work that assorts divergent isotype-specific PC function across four major modules of immune protection. Signals eliciting class-switch recombination can also imprint transcriptional changes in B cells retained through terminal differentiation. B cell class can influence cell fate determination and effector function. Class-linked PC effector function appears to sort according to the four broad categories of immune protection. Single-cell analysis allows increased dissection of B cell heterogeneity.