National Academy of Sciences, Proceedings of the National Academy of Sciences, 2(118), 2021
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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.