Affinity maturation without germinal centres in lymphotoxin-alpha-deficient mice.
Affinity maturation by somatic hypermutation is thought to occur within germinal centres. Mice deficient in lymphotoxin-alpha (LT alpha-/- mice) have no lymph nodes or Peyer's patches, and fail to form germinal centres in the spleen. We tested whether germinal centres are essential for maturation of antibody responses to T-cell-dependent antigens. LT alpha-/- mice immunized with low doses of (4-hydroxy-3-nitrophenyl)acetyl-ovalbumin (NP-OVA) showed dramatically impaired production of high-affinity anti-NP IgG1. However, LT alpha-/- mice immunized with high doses of NP-OVA, even though they failed to produce germinal centres, manifested a high-affinity anti-NP IgG1 response similar to wild-type mice. Furthermore, when LT alpha-/- mice were multiply immunized with high doses of NP-OVA, the predominantly expressed anti-NP VH gene segment VH186.2 showed somatic mutations typical of affinity maturation. Thus, B-cell memory and affinity maturation are not absolutely dependent on the presence of germinal centres.
Matsumoto
M
M
Center for Immunology and Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Lo
S F
SF
Carruthers
C J
CJ
Min
J
J
Mariathasan
S
S
Huang
G
G
Plas
D R
DR
Martin
S M
SM
Geha
R S
RS
Nahm
M H
MH
Chaplin
D D
DD
D000595:Amino Acid Sequence; D000818:Animals; D000915:Antibody Affinity / Q000276:immunology*; D000917:Antibody Formation / Q000276:immunology*; D000937:Antigen-Antibody Reactions; D000941:Antigens / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D001483:Base Sequence; D004247:DNA; D003713:Dendritic Cells / Q000502:physiology; D004306:Dose-Response Relationship, Immunologic; D018858:Germinal Center / Q000166:cytology / Q000276:immunology*; D007114:Immunization; D007074:Immunoglobulin G / Q000276:immunology; D007143:Immunoglobulin Heavy Chains / Q000235:genetics / Q000276:immunology; D007147:Immunoglobulin Light Chains / Q000235:genetics / Q000276:immunology; D007156:Immunologic Memory; D008233:Lymphotoxin-alpha / Q000276:immunology*; D051379:Mice; D008969:Molecular Sequence Data; D009596:Nitrophenols / Q000008:administration & dosage / Q000276:immunology; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D010648:Phenylacetates; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
D000941:Antigens; D007074:Immunoglobulin G; D007143:Immunoglobulin Heavy Chains; D007147:Immunoglobulin Light Chains; D008233:Lymphotoxin-alpha; D009596:Nitrophenols; D010648:Phenylacetates; C026242:4-hydroxy-5-nitrophenyl acetic acid; D010047:Ovalbumin; D004247:DNA