Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence
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Animals
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Antibody Affinity / immunology*
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Antibody Formation / immunology*
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Antigen-Antibody Reactions
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Antigens / immunology
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B-Lymphocytes / immunology*
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Base Sequence
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DNA
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Dendritic Cells / physiology
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Dose-Response Relationship, Immunologic
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Germinal Center / cytology
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Germinal Center / immunology*
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Immunization
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Immunoglobulin G / immunology
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Immunoglobulin Heavy Chains / genetics
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Immunoglobulin Heavy Chains / immunology
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Immunoglobulin Light Chains / genetics
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Immunoglobulin Light Chains / immunology
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Immunologic Memory
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Lymphotoxin-alpha / immunology*
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Mice
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Molecular Sequence Data
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Nitrophenols / administration & dosage
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Nitrophenols / immunology
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Ovalbumin / administration & dosage
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Ovalbumin / immunology
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Phenylacetates
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Spleen / cytology
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Spleen / immunology
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T-Lymphocytes / immunology*
Substances
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Antigens
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Immunoglobulin G
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Immunoglobulin Heavy Chains
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Immunoglobulin Light Chains
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Lymphotoxin-alpha
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Nitrophenols
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Phenylacetates
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4-hydroxy-5-nitrophenyl acetic acid
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Ovalbumin
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DNA