Antigen persistence is required for somatic mutation and affinity maturation of immunoglobulin

Yang Wang, Guangming Huang, Jing Wang, Hector Molina, David D. Chaplin, Yang Xin Fu

Research output: Contribution to journalArticlepeer-review

49 Scopus citations

Abstract

Whether germinal centers (GC) with follicular dendritic cell (FDC) clusters are the essential sites for affinity maturation of immunoglobulin is still controversial. To re-evaluate the role of GC/FDC in affinity maturation and somatic mutation in a defined antigen system, lymphotoxin-α-(/)- and TNF receptor I-(/)- mice, lacking GC/FDC, were immunized with (4-hydroxy-3-nitrophenyl) acetyl-sheep RBC (NP-SRBC). In contrast to soluble hapten-carrier systems, NP-SRBC allows us to compare affinity maturation in the presence or absence of adjuvant. These mice showed a dramatically impaired ability to generate high-affinity IgG to NP, but retained the ability to produce low-affinity anti-NP IgG when NP-SRBC was used in the absence of adjuvant. In contrast to wild-type mice, somatic mutation of the expressed IgG heavy chain gene was rarely detected in these GC/FDC-deficient mice. This suggests that GC/FDC are essential for affinity maturation. Trapping antigen-specific B cells inside the T cell zone of TNFRI-(/)- mice may prolong the interaction between T and B cells, which allows class switching but no further affinity maturation of IgG. Interestingly, GC/FDC-deficient mice could be induced to generate high-affinity, somatically mutated IgG antibodies by immunization with the same amount of NP-SRBC antigen emulsified in incomplete Freund's adjuvant or repeated immunization with the antigen alone. Thus, these data support a model in which prolonged availability of antigen is required for somatic mutation and affinity maturation, and FDC or adjuvants facilitate such processes by slowly releasing antigens.

Original languageEnglish
Pages (from-to)2226-2234
Number of pages9
JournalEuropean Journal of Immunology
Volume30
Issue number8
DOIs
StatePublished - 2000

Keywords

  • Affinity maturation
  • Follicular dendritic cell
  • Germinal center
  • Lymphotoxin
  • Tumor

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