TY - JOUR
T1 - Antigen persistence is required for somatic mutation and affinity maturation of immunoglobulin
AU - Wang, Yang
AU - Huang, Guangming
AU - Wang, Jing
AU - Molina, Hector
AU - Chaplin, David D.
AU - Fu, Yang Xin
PY - 2000
Y1 - 2000
N2 - 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.
AB - 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.
KW - Affinity maturation
KW - Follicular dendritic cell
KW - Germinal center
KW - Lymphotoxin
KW - Tumor
UR - http://www.scopus.com/inward/record.url?scp=0033838426&partnerID=8YFLogxK
U2 - 10.1002/1521-4141(2000)30:8<2226::AID-IMMU2226>3.0.CO;2-5
DO - 10.1002/1521-4141(2000)30:8<2226::AID-IMMU2226>3.0.CO;2-5
M3 - Article
C2 - 10940914
AN - SCOPUS:0033838426
SN - 0014-2980
VL - 30
SP - 2226
EP - 2234
JO - European Journal of Immunology
JF - European Journal of Immunology
IS - 8
ER -