T cell help controls the speed of the cell cycle in germinal center B cells

• Autores: Alexander D. Gitlin, Christian T. Mayer, Thiago Y. Oliveira
• Localización: Science, ISSN 0036-8075, Vol. 349, Nº 6248, 2015, págs. 643-646
• Idioma: inglés
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• Resumen

  • The germinal center (GC) is a microanatomical compartment wherein high-affinity antibody-producing B cells are selectively expanded. B cells proliferate and mutate their antibody genes in the dark zone (DZ) of the GC and are then selected by T cells in the light zone (LZ) on the basis of affinity. Here, we show that T cell help regulates the speed of cell cycle phase transitions and DNA replication of GC B cells. Genome sequencing and single-molecule analyses revealed that T cell help shortens S phase by regulating replication fork progression, while preserving the relative order of replication origin activation. Thus, high-affinity GC B cells are selected by a mechanism that involves prolonged dwell time in the DZ where selected cells undergo accelerated cell cycles.