Somatic mutation of immunoglobulin V(H)6 genes in human infants. 1998

J Ridings, and L Dinan, and R Williams, and D Roberton, and H Zola
Child Health Research Institute, Department of Paediatrics, University of Adelaide, South Australia.

Infants respond to antigen by making antibody that is generally of low affinity for antigen. Somatic hypermutation of immunoglobulin genes, and selection of cells expressing mutations with improved affinity for antigen, are the molecular and cellular processes underlying the maturation of antibody affinity. We have reported previously that neonates and infants up to 2 months of age, including individuals undergoing strong immunological challenge, show very few mutated V(H)6 sequences, with low mutation frequencies in mutated sequences, and little evidence of selection. We have now examined immunoglobulin genes from healthy infants between 2 and 10 months old for mutation and evidence of selection. In this age group, the proportion of V(H)6 sequences which are mutated and the mutation frequency in mutated sequences increase with age. There is evidence of selection from 6 months old. These results indicate that the process of affinity maturation, which depends on cognate T-B cell interaction and functional germinal centres, is approaching maturity from 6 months old.

UI MeSH Term Description Entries
D007135 Immunoglobulin Variable Region That region of the immunoglobulin molecule that varies in its amino acid sequence and composition, and comprises the binding site for a specific antigen. It is located at the N-terminus of the Fab fragment of the immunoglobulin. It includes hypervariable regions (COMPLEMENTARITY DETERMINING REGIONS) and framework regions. Variable Region, Ig,Variable Region, Immunoglobulin,Framework Region, Immunoglobulin,Fv Antibody Fragments,Fv Fragments,Ig Framework Region,Ig Variable Region,Immunoglobulin Framework Region,Immunoglobulin Fv Fragments,Immunoglobulin V,Antibody Fragment, Fv,Antibody Fragments, Fv,Fragment, Fv,Fragment, Fv Antibody,Fragment, Immunoglobulin Fv,Fragments, Fv,Fragments, Fv Antibody,Fragments, Immunoglobulin Fv,Framework Region, Ig,Framework Regions, Ig,Framework Regions, Immunoglobulin,Fv Antibody Fragment,Fv Fragment,Fv Fragment, Immunoglobulin,Fv Fragments, Immunoglobulin,Ig Framework Regions,Ig Variable Regions,Immunoglobulin Framework Regions,Immunoglobulin Fv Fragment,Immunoglobulin Variable Regions,Regions, Immunoglobulin Variable,Variable Regions, Ig,Variable Regions, Immunoglobulin
D007137 Immunoglobulin alpha-Chains The class of heavy chains found in IMMUNOGLOBULIN A. They have a molecular weight of approximately 58 kDa and contain about 470 amino acid residues arranged in four domains and an oligosaccharide component bound covalently to their Fc fragment constant region. Ig alpha Chains,Immunoglobulins, alpha-Chain,Immunoglobulin alpha-Chain,alpha-Chain Immunoglobulins,alpha-Immunoglobulin Heavy Chain,alpha-Immunoglobulin Heavy Chains,Chains, Ig alpha,Heavy Chain, alpha-Immunoglobulin,Heavy Chains, alpha-Immunoglobulin,Immunoglobulin alpha Chain,Immunoglobulin alpha Chains,Immunoglobulins, alpha Chain,alpha Chain Immunoglobulins,alpha Chains, Ig,alpha Immunoglobulin Heavy Chain,alpha Immunoglobulin Heavy Chains,alpha-Chain, Immunoglobulin,alpha-Chains, Immunoglobulin
D007143 Immunoglobulin Heavy Chains The largest of polypeptide chains comprising immunoglobulins. They contain 450 to 600 amino acid residues per chain, and have molecular weights of 51-72 kDa. Immunoglobulins, Heavy-Chain,Heavy-Chain Immunoglobulins,Ig Heavy Chains,Immunoglobulin Heavy Chain,Immunoglobulin Heavy Chain Subgroup VH-I,Immunoglobulin Heavy Chain Subgroup VH-III,Heavy Chain Immunoglobulins,Heavy Chain, Immunoglobulin,Heavy Chains, Ig,Heavy Chains, Immunoglobulin,Immunoglobulin Heavy Chain Subgroup VH I,Immunoglobulin Heavy Chain Subgroup VH III,Immunoglobulins, Heavy Chain
D007223 Infant A child between 1 and 23 months of age. Infants
D009154 Mutation Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations. Mutations
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000328 Adult A person having attained full growth or maturity. Adults are of 19 through 44 years of age. For a person between 19 and 24 years of age, YOUNG ADULT is available. Adults
D014644 Genetic Variation Genotypic differences observed among individuals in a population. Genetic Diversity,Variation, Genetic,Diversity, Genetic,Diversities, Genetic,Genetic Diversities,Genetic Variations,Variations, Genetic
D022801 Complementarity Determining Regions Three regions (CDR1; CDR2 and CDR3) of amino acid sequence in the IMMUNOGLOBULIN VARIABLE REGION that are highly divergent. Together the CDRs from the light and heavy immunoglobulin chains form a surface that is complementary to the antigen. These regions are also present in other members of the immunoglobulin superfamily, for example, T-cell receptors (RECEPTORS, ANTIGEN, T-CELL). Complementarity Determining Region,Complementarity Determining Region 1,Complementarity Determining Region 2,Complementarity Determining Region 3,Complementarity Determining Region I,Complementarity Determining Region II,Complementarity Determining Region III,Complementarity-Determining Region,Complementarity-Determining Region 3,Hypervariable Region, Immunoglobulin,Hypervariable Regions, Immunoglobulin,Third Complementarity-Determining Region,Complementarity-Determining Region 3s,Complementarity-Determining Region, Third,Complementarity-Determining Regions,Complementarity-Determining Regions, Third,Immunoglobulin Hypervariable Region,Immunoglobulin Hypervariable Regions,Region, Complementarity Determining,Region, Immunoglobulin Hypervariable,Regions, Complementarity Determining,Regions, Complementarity-Determining,Regions, Immunoglobulin Hypervariable,Third Complementarity Determining Region,Third Complementarity-Determining Regions

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