Continuous germinal center invasion contributes to the diversity of the immune response.
antibody affinity
antibody diversity
germinal center
Journal
Cell
ISSN: 1097-4172
Titre abrégé: Cell
Pays: United States
ID NLM: 0413066
Informations de publication
Date de publication:
05 01 2023
05 01 2023
Historique:
received:
13
04
2022
revised:
12
09
2022
accepted:
28
11
2022
pmc-release:
05
01
2024
pubmed:
25
12
2022
medline:
11
1
2023
entrez:
24
12
2022
Statut:
ppublish
Résumé
Antibody responses are characterized by increasing affinity and diversity over time. Affinity maturation occurs in germinal centers by a mechanism that involves repeated cycles of somatic mutation and selection. How antibody responses diversify while also undergoing affinity maturation is not as well understood. Here, we examined germinal center (GC) dynamics by tracking B cell entry, division, somatic mutation, and specificity. Our experiments show that naive B cells continuously enter GCs where they compete for T cell help and undergo clonal expansion. Consistent with late entry, invaders carry fewer mutations but can contribute up to 30% or more of the cells in late-stage germinal centers. Notably, cells entering the germinal center at later stages of the reaction diversify the immune response by expressing receptors that show low affinity to the immunogen. Paradoxically, the affinity threshold for late GC entry is lowered in the presence of high-affinity antibodies.
Identifiants
pubmed: 36565698
pii: S0092-8674(22)01507-0
doi: 10.1016/j.cell.2022.11.032
pmc: PMC9825658
mid: NIHMS1854161
pii:
doi:
Substances chimiques
Antigens
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
147-161.e15Subventions
Organisme : NIAID NIH HHS
ID : T32 AI070084
Pays : United States
Organisme : NIAID NIH HHS
ID : P01 AI100148
Pays : United States
Organisme : NIAID NIH HHS
ID : P01 AI138938
Pays : United States
Organisme : NIAID NIH HHS
ID : P01 AI138212
Pays : United States
Organisme : NIAID NIH HHS
ID : R37 AI037526
Pays : United States
Organisme : NIAID NIH HHS
ID : U19 AI111825
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI037526
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI144462
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests The Rockefeller University has filed a provisional patent application in connection with C135 and C144 antibodies used in this work, on which M.C.N. is an inventor (US patent 63/021,387).
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