Affinity maturation of antibody responses is mediated by differential plasma cell proliferation

Increased antibody affinity over time after vaccination is a prototypical feature of immune responses. Recent studies have shown that a diverse collection of B cells, producing antibodies with a wide spectrum of different affinities, are selected into the plasma cell (PC) pathway. How affinity-permissive selection enables PC affinity maturation remains unknown. Here we report that PC precursors (prePC) expressing high affinity antibodies received higher levels of T follicular helper (Tfh) and divided at higher rates than their lower affinity counterparts once they left the GC. Thus, differential cell division by selected prePCs accounted for how diverse precursors developed into a PC compartment that mediated serological affinity maturation. S1PR2-CreERT2 R26 ZsG mice were immunized with the hapten-carrier NP-OVA followed by tamoxifen administration 5 days after immunization. ZsG labeled Fas+ GL7+ CD38- GC B cells and their progeny B220- CD138+ TACI+ were sorted 14 days after immunzation. Multiplexed mouse samples: M1-M6.