title: HUMORAL IMMUNITY. T cell help controls the speed of the cell cycle in germinal center B cells.
abstract: 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.
authors.affiliation: Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA.
authors.forename: Alexander D
authors.initials: AD
authors.lastname: Gitlin
authors.affiliation: Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA.
authors.forename: Christian T
authors.initials: CT
authors.lastname: Mayer
authors.affiliation: Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA.
authors.forename: Thiago Y
authors.initials: TY
authors.lastname: Oliveira
authors.affiliation: Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA.
authors.forename: Ziv
authors.initials: Z
authors.lastname: Shulman
authors.affiliation: Molecular Biology Program, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA.
authors.forename: Mathew J K
authors.initials: MJ
authors.lastname: Jones
authors.affiliation: Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Amnon
authors.initials: A
authors.lastname: Koren
authors.affiliation: Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA. Howard Hughes Medical Institute (HHMI), The Rockefeller University, New York, NY 10065, USA. nussen@rockefeller.edu.
authors.forename: Michel C
authors.initials: MC
authors.lastname: Nussenzweig
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology*; D002453:Cell Cycle / Q000235:genetics / Q000276:immunology*; D049109:Cell Proliferation; D004261:DNA Replication / Q000235:genetics / Q000276:immunology*; D005786:Gene Expression Regulation; D018858:Germinal Center / Q000166:cytology*; D056724:Immunity, Humoral / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D016196:S Phase / Q000235:genetics / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*