Clonal selection in the germinal centre by regulated proliferation and hypermutation
TLDR
It is found 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.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.read more
Citations
More filters
Journal ArticleDOI
T follicular helper cell differentiation, function, and roles in disease
TL;DR: There has been dramatic advances in this young field, but there is much to be learned about Tfh cell biology in the interest of applying that knowledge to biomedical needs.
Journal ArticleDOI
The generation of antibody-secreting plasma cells.
TL;DR: The regulation of antibody production is linked to the generation and maintenance of plasmablasts and plasma cells from their B cell precursors, and the terminal differentiation of B cells can be described as a simple probabilistic process governed by a central gene-regulatory network and modified by environmental stimuli.
Journal ArticleDOI
Follicular Helper T Cells
TL;DR: The realization that follicular T cells are heterogeneous, comprising helper and regulatory subsets, has raised questions regarding a possible division of labor in germinal center B cell selection and elimination.
Journal ArticleDOI
T Follicular Helper Cell Biology: A Decade of Discovery and Diseases
TL;DR: Advances in the understanding of Tfh cell differentiation and function are discussed, as are theUnderstanding of T fh cells in infectious diseases, vaccines, autoimmune diseases, allergies, atherosclerosis, organ transplants, and cancer.
Journal ArticleDOI
Dynamics of B cells in germinal centres
Nilushi S. De Silva,Ulf Klein +1 more
TL;DR: This Review focuses on recent studies that uncovered crucial cues that are required for the formation and the maintenance of GCs and for the selection of high-affinity antibody mutants and its implications for the establishment of humoral immunity.
References
More filters
Journal ArticleDOI
Defining the epithelial stem cell niche in skin.
Tudorita Tumbar,Géraldine Guasch,Valentina Greco,Cédric Blanpain,William E. Lowry,Michael Rendl,Elaine Fuchs +6 more
TL;DR: It is found that these cells rarely divide within their niche but change properties abruptly when stimulated to exit, and their transcriptional profile is determined, which, when compared to progeny and other SCs, defines the niche.
Journal ArticleDOI
Clonal selection and learning in the antibody system
TL;DR: A second selection process occurs during immune responses in which a new antibody repertoire is generated through somatic hypermutation, where only mutants binding antigen with high affinity survive to become memory cells.
Journal ArticleDOI
Intraclonal generation of antibody mutants in germinal centres
TL;DR: Direct evidence is reported for direct evidence that antigen-induced proliferation of B cells at another site, periarteriolar lymphocyte sheath-associated foci, was not associated with somatic hypermutation, and most represent cells of distinct B-cell clones which expanded locally, generating somatic antibody mutants at high rate.
Journal ArticleDOI
Germinal center dynamics revealed by multiphoton microscopy with a photoactivatable fluorescent reporter.
Gabriel D. Victora,Tanja A. Schwickert,David R. Fooksman,Alice O. Kamphorst,Michael Meyer-Hermann,Michael L. Dustin,Michel C. Nussenzweig,Michel C. Nussenzweig +7 more
TL;DR: It is found that B cell division is restricted to the DZ, with a net vector of B cell movement from the D Z to the LZ, and T cell help, and not direct competition for antigen, is the limiting factor in GC selection.
Journal ArticleDOI
The receptor DEC-205 expressed by dendritic cells and thymic epithelial cells is involved in antigen processing
Wanping Jiang,William J. Swiggard,Christine Heufler,Christine Heufler,Michael Peng,Asra Mirza,Ralph M. Steinman,Michel C. Nussenzweig,Michel C. Nussenzweig +8 more
TL;DR: DEC-205 is a novel endocytic receptor that can be used by dendritic cells and thymic epithelial cells to direct captured antigens from the extracellular space to a specialized antigen-processing compartment.