Mechanisms Promoting Stability of B Cells

Upon activation, B cells integrate signals from antigen and T cell help to choose between a rapid extrafollicular (EF) response and entry into the germinal center (GC). EF differentiation produces short-lived plasmablasts that provide immediate but relatively low-affinity antibody, whereas GC entry commits B cells to iterative selection, somatic hypermutation, and affinity maturation, ultimately yielding high-affinity plasma cells and memory B cells. At the B-T cell border, where both responses originate, B cells also undergo class switch recombination (CSR). In this review, we examine the molecular mechanisms of CSR, highlighting the interplay between the DNA deaminase AID, transcription, and noncanonical nucleic acid structures. We further discuss the differential requirement of glycolysis between the EF versus GC response and how the cytokine IL-21 fine-tunes B cell entry into the GC. Together, these perspectives integrate genomic alterations, metabolic demands, and cytokine-mediated signaling at the critical decision point between EF and GC pathways.