Role of affinity in plasma cell development in the germinal center light zone. Role of affinity in plasma cell development in the germinal center light zone

Protective immune responses to many pathogens depend on the development of high affinity antibody-producing plasma cells in germinal centers. Transgenic models suggest that there is a stringent affinity-based barrier to plasma cell development. Whether a similar high affinity barrier regulates plasma cell development under physiologic circumstances, and the nature of the plasma cell fate decision has not been defined precisely. Here we use a fate mapping approach to examine the relationship between germinal center (GC) B cells selected to undergo additional rounds of affinity maturation, germinal center pre-plasma cells and plasma cells. The data show that initial plasma cell selection overlaps with germinal center B cell selection, but that the plasma cell 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-plasma cell selection sieves the germinal center to enable accumulation of a more restricted group of high affinity antibody secreting plasma cells. Overall design: c-Myc-GFP or C57Bl6/J male mice were immunized with NP-Ova in Alhydrogel and GC B cells (LZ and DZ) and Plasma cells were FACS-sorted on day 14