Role of affinity in plasma cell development in the germinal center light zone
Mohamed ElTanbouly, Víctor Ramos, Andrew J. MacLean, Spencer T. Chen, Maximilian Loewe, Sandra Steinbach, Tarek Ben Tanfous, Brianna Johnson, Melissa Cipolla, Anna Gazumyan, Thiago Y. Oliveira, Michel C. Nussenzweig
Abstract
Protective immune responses to many pathogens depend on the development of high-affinity antibody-producing plasma cells (PC) in germinal centers (GCs). Transgenic models suggest that there is a stringent affinity-based barrier to PC development. Whether a similar high-affinity barrier regulates PC development under physiologic circumstances and the nature of the PC fate decision has not been defined precisely. Here, we use a fate-mapping approach to examine the relationship between GC B cells selected to undergo additional rounds of affinity maturation, GC pre-PC, and PC. The data show that initial PC selection overlaps with GC B cell selection, but that the PC compartment accumulates a less diverse and higher affinity collection of antibodies over time. Thus, whereas the GC continues to diversify over time, affinity-based pre-PC selection sieves the GC to enable the accumulation of a more restricted group of high-affinity antibody-secreting PC.