Clonal selection in the germinal centre by regulated proliferation and hypermutation.

TitleClonal selection in the germinal centre by regulated proliferation and hypermutation.
Publication TypeJournal Article
Year of Publication2014
AuthorsGitlin AD, Shulman, iv Z, Nussenzweig MC
JournalNature
Volume509
Issue7502
Pagination637-40
Date Published05/29/2014
ISSN1476-4687
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.

DOI10.1038/nature13300
Alternate JournalNature
PubMed ID24805232
Grant List1UM1 AI100663-01 / AI / NIAID NIH HHS / United States
AI037526-19 / AI / NIAID NIH HHS / United States
AI072529-06 / AI / NIAID NIH HHS / United States
T32GM07739 / GM / NIGMS NIH HHS / United States
/ / Howard Hughes Medical Institute / United States
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