title: Clonal selection in the germinal centre by regulated proliferation and hypermutation.
abstract: During immune responses, B lymphocytes clonally expand and undergo secondary diversification of their immunoglobulin genes in germinal centres (GCs). High-affinity B cells are expanded through iterative interzonal cycles of division and hypermutation in the GC dark zone followed by migration to the GC light zone, where they are selected on the basis of affinity to return to the dark zone. Here we combine a transgenic strategy to measure cell division and a photoactivatable fluorescent reporter to examine whether the extent of clonal expansion and hypermutation are regulated during interzonal GC cycles. We find that both cell division and hypermutation are directly proportional to the amount of antigen captured and presented by GC B cells to follicular helper T cells in the light zone. Our data explain how GC B cells with the highest affinity for antigen are selectively expanded and diversified.
authors.affiliation: Laboratory of Molecular Immunology, The Rockefeller University, New York, New York 10065, USA.
authors.forename: Alexander D
authors.initials: AD
authors.lastname: Gitlin
authors.affiliation: Laboratory of Molecular Immunology, The Rockefeller University, New York, New York 10065, USA.
authors.forename: Ziv
authors.initials: Z
authors.lastname: Shulman
authors.affiliation: 1] Laboratory of Molecular Immunology, The Rockefeller University, New York, New York 10065, USA [2] Howard Hughes Medical Institute, The Rockefeller University, New York, New York 10065, USA.
authors.forename: Michel C
authors.initials: MC
authors.lastname: Nussenzweig
mesh_terms: D000818:Animals; D000915:Antibody Affinity / Q000276:immunology; D017951:Antigen Presentation / Q000276:immunology; D000941:Antigens / Q000276:immunology; D001402:B-Lymphocytes / Q000166:cytology* / Q000276:immunology / Q000378:metabolism*; D002465:Cell Movement; D049109:Cell Proliferation; D060966:Clonal Selection, Antigen-Mediated / Q000276:immunology; D002999:Clone Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D017930:Genes, Reporter / Q000235:genetics; D018858:Germinal Center / Q000166:cytology* / Q000276:immunology*; D008297:Male; D051379:Mice; D016196:S Phase; D027041:Somatic Hypermutation, Immunoglobulin / Q000235:genetics*; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology / Q000276:immunology; D013997:Time Factors
chemical_list: D000941:Antigens