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

Citation
Y. Wang et al., Antigen persistence is required for somatic mutation and affinity maturation of immunoglobulin, EUR J IMMUN, 30(8), 2000, pp. 2226-2234
Citations number
33
Categorie Soggetti
Immunology
Journal title
EUROPEAN JOURNAL OF IMMUNOLOGY
ISSN journal
00142980 → ACNP
Volume
30
Issue
8
Year of publication
2000
Pages
2226 - 2234
Database
ISI
SICI code
0014-2980(200008)30:8<2226:APIRFS>2.0.ZU;2-8
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 an d somatic mutation in a defined antigen system, lymphotoxin-alpha(-/-) and TNF receptor I-/- mice, lacking GC/FDC, were immunized with (4-hydroxy-3-ni trophenyl) acetyl-sheep RBC (NP-SRBC). In contrast to soluble hapten-carrie r 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 lo w-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 ch ain gene was rarely detected in these GC/FDC-deficient mice. This suggests that GC/FDC are essential for affinity maturation. Trapping antigen-specifi c B cells inside the T cell zone of TNFRI-/- mice may prolong the interacti on between T and B cells, which allows class switching but no further affin ity maturation of IgG. Interestingly, GC/FDC-deficient mice could be induce d to generate high-affinity, somatically mutated IgG antibodies by immuniza tion with the same amount of NP-SRBC antigen emulsified in incomplete Freun d's adjuvant or repeated immunization with the antigen alone. Thus, these d ata support a model in which prolonged availability of antigen is required for somatic mutation and affinity maturation, and FDC or adjuvants facilita te such processes by slowly releasing antigens.