Differentiation of germinal center B cells into plasma cells is initiated by high-affinity antigen and completed by Tfh cells.
Nike Julia Krautler,Dan Suan,Danyal Butt,Katherine Bourne,Jana R. Hermes,Tyani D. Chan,Tyani D. Chan,Christopher Sundling,Warren Kaplan,Warren Kaplan,Peter R. Schofield,Jennifer Jackson,Antony Basten,Antony Basten,Daniel Christ,Daniel Christ,Robert Brink,Robert Brink +17 more
TLDR
It is shown that differentiation into PCs is induced among a discrete subset of high-affinity B cells residing within the light zone of the GC, which has likely evolved to both sustain protective immunity and avoid autoantibody production.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.read more
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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.
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B Cell Responses: Cell Interaction Dynamics and Decisions
TL;DR: How basic research is informing efforts to generate vaccines that induce broadly neutralizing antibodies against viral pathogens is discussed, revealing the special features associated with allergen-reactive IgE responses and uncovering the antibody-independent mechanisms by which B cells contribute to health and disease.
Journal ArticleDOI
T Follicular Helper Cell-Germinal Center B Cell Interaction Strength Regulates Entry into Plasma Cell or Recycling Germinal Center Cell Fate
Wataru Ise,Kentaro Fujii,Katsuyuki Shiroguchi,Ayako Ito,Kohei Kometani,Kiyoshi Takeda,Eiryo Kawakami,Kazuo Yamashita,Kazuhiro Suzuki,Takaharu Okada,Tomohiro Kurosaki +10 more
TL;DR: The data support a model whereby commitment to the plasma cell begins in the GC and suggest that stability of Tfh‐GC B cell contacts is key for plasma cell‐prone GC cell formation.
Journal ArticleDOI
BAFF and BAFF-Receptor in B Cell Selection and Survival.
TL;DR: BAFFR deficiency in humans is characterized by very few circulating B cells, very low IgM and IgG serum concentrations but normal or high IgA levels, which is different from mutations affecting pathway components coupled to B cell antigen receptor (BCR) signaling.
Journal ArticleDOI
CCR6 Defines Memory B Cell Precursors in Mouse and Human Germinal Centers, Revealing Light-Zone Location and Predominant Low Antigen Affinity
Dan Suan,Dan Suan,Nike Julia Krautler,Nike Julia Krautler,Jesper L.V. Maag,Danyal Butt,Katherine Bourne,Jana R. Hermes,Danielle T. Avery,Clara Young,Aaron L. Statham,Michael Elliott,Marcel E. Dinger,Marcel E. Dinger,Antony Basten,Antony Basten,Stuart G. Tangye,Stuart G. Tangye,Robert Brink,Robert Brink +19 more
TL;DR: It is reported that the chemokine receptor CCR6 uniquely marks MBC precursors in both mouse and human GCs, which indicate a fundamental dichotomy between the processes that drive MBC and PC differentiation during GC responses.
References
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