title: Differentiation of germinal center B cells into plasma cells is initiated by high-affinity antigen and completed by Tfh cells.
abstract: Plasma cells (PCs) derived from germinal centers (GCs) secrete the high-affinity antibodies required for long-term serological immunity. Nevertheless, the process whereby GC B cells differentiate into PCs is uncharacterized, and the mechanism underlying the selective PC differentiation of only high-affinity GC B cells remains unknown. In this study, we show that differentiation into PCs is induced among a discrete subset of high-affinity B cells residing within the light zone of the GC. Initiation of differentiation required signals delivered upon engagement with intact antigen. Signals delivered by T follicular helper cells were not required to initiate differentiation but were essential to complete the differentiation process and drive migration of maturing PCs through the dark zone and out of the GC. This bipartite or two-signal mechanism has likely evolved to both sustain protective immunity and avoid autoantibody production.
authors.affiliation: Immunology Division, Garvan Institute of Medical Research, Darlinghurst NSW 2010, Australia.
authors.forename: Nike J
authors.identifier: 0000-0003-2014-5971
authors.initials: NJ
authors.lastname: Kräutler
authors.affiliation: Immunology Division, Garvan Institute of Medical Research, Darlinghurst NSW 2010, Australia.
authors.forename: Dan
authors.identifier: 0000-0001-5996-5120
authors.initials: D
authors.lastname: Suan
authors.affiliation: Immunology Division, Garvan Institute of Medical Research, Darlinghurst NSW 2010, Australia.
authors.forename: Danyal
authors.identifier: 0000-0001-8191-2025
authors.initials: D
authors.lastname: Butt
authors.affiliation: Immunology Division, Garvan Institute of Medical Research, Darlinghurst NSW 2010, Australia.
authors.forename: Katherine
authors.initials: K
authors.lastname: Bourne
authors.affiliation: Immunology Division, Garvan Institute of Medical Research, Darlinghurst NSW 2010, Australia.
authors.forename: Jana R
authors.initials: JR
authors.lastname: Hermes
authors.affiliation: Immunology Division, Garvan Institute of Medical Research, Darlinghurst NSW 2010, Australia.|St. Vincent's Clinical School, University of New South Wales, Darlinghurst NSW 2010, Australia.
authors.forename: Tyani D
authors.initials: TD
authors.lastname: Chan
authors.affiliation: Immunology Division, Garvan Institute of Medical Research, Darlinghurst NSW 2010, Australia.
authors.forename: Christopher
authors.identifier: 0000-0002-6138-690X
authors.initials: C
authors.lastname: Sundling
authors.affiliation: Kinghorn Centre for Clinical Genomics, Garvan Institute of Medical Research, Darlinghurst NSW 2010, Australia.|St. Vincent's Clinical School, University of New South Wales, Darlinghurst NSW 2010, Australia.
authors.forename: Warren
authors.initials: W
authors.lastname: Kaplan
authors.affiliation: Immunology Division, Garvan Institute of Medical Research, Darlinghurst NSW 2010, Australia.
authors.forename: Peter
authors.initials: P
authors.lastname: Schofield
authors.affiliation: Immunology Division, Garvan Institute of Medical Research, Darlinghurst NSW 2010, Australia.
authors.forename: Jennifer
authors.identifier: 0000-0003-4237-5233
authors.initials: J
authors.lastname: Jackson
authors.affiliation: Immunology Division, Garvan Institute of Medical Research, Darlinghurst NSW 2010, Australia.|St. Vincent's Clinical School, University of New South Wales, Darlinghurst NSW 2010, Australia.
authors.forename: Antony
authors.identifier: 0000-0003-2200-7695
authors.initials: A
authors.lastname: Basten
authors.affiliation: Immunology Division, Garvan Institute of Medical Research, Darlinghurst NSW 2010, Australia.|St. Vincent's Clinical School, University of New South Wales, Darlinghurst NSW 2010, Australia.
authors.forename: Daniel
authors.initials: D
authors.lastname: Christ
authors.affiliation: Immunology Division, Garvan Institute of Medical Research, Darlinghurst NSW 2010, Australia r.brink@garvan.org.au.|St. Vincent's Clinical School, University of New South Wales, Darlinghurst NSW 2010, Australia.
authors.forename: Robert
authors.identifier: 0000-0002-9586-3655
authors.initials: R
authors.lastname: Brink
mesh_terms: D000818:Animals; D000944:Antigens, Differentiation, B-Lymphocyte / Q000502:physiology*; D001402:B-Lymphocytes / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology*; D018858:Germinal Center / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D010950:Plasma Cells / Q000502:physiology*; D006377:T-Lymphocytes, Helper-Inducer / Q000502:physiology*
chemical_list: D000944:Antigens, Differentiation, B-Lymphocyte