Continuous germinal center invasion contributes to the diversity of the immune response

• DOI: 10.1016/j.cell.2022.11.032
• Publication Date: 2022-12-23T15:29:06Z
• Authors: Thomas Hägglöf; Melissa Cipolla; Maximilian Loewe; Spencer T. Chen; Ervin E. Kara; Luka Mesin; Harald Hartweger; Mohamed A. ElTanb...; Alice Cho; Anna Gazumyan; Victor Ramos; Leonidas Stamatatos; Thiago Y. Oliveira; Michel C. Nussenz...; Charlotte Viant
• Keywords: Affinity maturation; Immunogen

Antibody responses are characterized by increasing affinity and diversity over time. Affinity maturation occurs in germinal centers a mechanism that involves repeated cycles of somatic mutation selection. How antibody diversify while also undergoing is not as well understood. Here, we examined center (GC) dynamics tracking B cell entry, division, mutation, specificity. Our experiments show naive cells continuously enter GCs where they compete for T help undergo clonal expansion. Consistent with late invaders carry fewer mutations but can contribute up to 30% or more the late-stage centers. Notably, entering at later stages reaction immune response expressing receptors low immunogen. Paradoxically, threshold GC entry lowered presence high-affinity antibodies.