Permissive selection followed by affinity-based proliferation of GC light zone B cells dictates cell fate and ensures clonal breadth
Rinako Nakagawa, Amparo Toboso-Navasa, Marta Schips, George R. Young, Leena Bhaw, Miriam Llorian, Probir Chakravarty, Abdul Karim Sesay, George Kassiotis, Michael Meyer‐Hermann, Dinis Pedro Calado
Abstract
Significance Light zone (LZ) B cells are selected in germinal centers (GCs) in a cMyc-dependent manner, before dark zone (DZ) migration. Antigen affinity of B cells is enhanced during GC responses, and some differentiate into plasmablasts or memory B cells (MBCs). Currently, GC selection is presumed as a competitive affinity-dependent process. This cannot explain retention of GC B cells with varied affinities. We identified cMyc + LZ B cell subpopulations enriched with either higher-affinity plasmablast precursors or lower-affinity MBC precursors and future DZ entrants, which diverged soon after permissive selection. Future DZ entrants’ affinity was enhanced through preferential proliferation of higher-affinity cells, and lower-affinity cells were retained in GCs. These findings elucidate mechanistically how GC selection ensures clonal diversity for broad protection.