title: The role of evolutionarily conserved germ-line DH sequence in B-1 cell development and natural antibody production.
abstract: Because of N addition and variation in the site of VDJ joining, the third complementarity-determining region of the heavy chain (CDR-H3) is the most diverse component of the initial immunoglobulin antigen-binding site repertoire. A large component of the peritoneal cavity B-1 cell component is the product of fetal and perinatal B cell production. The CDR-H3 repertoire is thus depleted of N addition, which increases dependency on germ-line sequence. Cross-species comparisons have shown that DH gene sequence demonstrates conservation of amino acid preferences by reading frame. Preference for reading frame 1, which is enriched for tyrosine and glycine, is created both by rearrangement patterns and by pre-BCR and BCR selection. In previous studies, we have assessed the role of conserved DH sequence by examining peritoneal cavity B-1 cell numbers and antibody production in BALB/c mice with altered DH loci. Here, we review our finding that changes in the constraints normally imposed by germ-line-encoded amino acids within the CDR-H3 repertoire profoundly affect B-1 cell development, especially B-1a cells, and thus natural antibody immunity. Our studies suggest that both natural and somatic selection operate to create a restricted B-1 cell CDR-H3 repertoire.
authors.affiliation: Program in Immunobiology, Carlos Chagas Filho Institute of Biophysics.
authors.forename: Andre M
authors.initials: AM
authors.lastname: Vale
authors.affiliation: Department of Immunology, Paulo de Goes Institute of Microbiology, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Alberto
authors.initials: A
authors.lastname: Nobrega
authors.affiliation: Department of Medicine.|Department of Microbiology.|Department of Genetics, University of Alabama at Birmingham, Birmingham, Alabama.
authors.forename: Harry W
authors.initials: HW
authors.lastname: Schroeder
mesh_terms: D000818:Animals; D000917:Antibody Formation / Q000502:physiology*; D016175:B-Lymphocyte Subsets / Q000502:physiology*; D022801:Complementarity Determining Regions / Q000502:physiology*; D017124:Conserved Sequence / Q000502:physiology*; D019143:Evolution, Molecular; D005854:Germ Cells / Q000502:physiology*; D006801:Humans
chemical_list: D022801:Complementarity Determining Regions
keywords: B-1 cell development; germ-line DH gene segment; natural antibody repertoire