title: High-throughput antibody sequencing reveals genetic evidence of global regulation of the naïve and memory repertoires that extends across individuals.
abstract: Vast diversity in the antibody repertoire is a key component of the adaptive immune response. This diversity is generated centrally through the assembly of variable, diversity and joining gene segments, and peripherally by somatic hypermutation and class-switch recombination. The peripheral diversification process is thought to only occur in response to antigenic stimulus, producing antigen-selected memory B cells. Surprisingly, analyses of the variable, diversity and joining gene segments have revealed that the naïve and memory subsets are composed of similar proportions of these elements. Lacking, however, is a more detailed study, analyzing the repertoires of naïve and memory subsets at the level of the complete V(D)J recombinant. This report presents a thorough examination of V(D)J recombinants in the human peripheral blood repertoire, revealing surprisingly large repertoire differences between circulating B-cell subsets and providing genetic evidence for global control of repertoire diversity in naïve and memory circulating B-cell subsets.
authors.affiliation: Departments of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232-0417, USA.
authors.forename: B S
authors.initials: BS
authors.lastname: Briney
authors.forename: J R
authors.initials: JR
authors.lastname: Willis
authors.forename: B A
authors.initials: BA
authors.lastname: McKinney
authors.forename: J E
authors.initials: JE
authors.lastname: Crowe
mesh_terms: D000328:Adult; D000916:Antibody Diversity / Q000235:genetics*; D016175:B-Lymphocyte Subsets / Q000276:immunology; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007074:Immunoglobulin G / Q000235:genetics; D007075:Immunoglobulin M / Q000235:genetics; D007156:Immunologic Memory / Q000235:genetics*; D060152:V(D)J Recombination
chemical_list: D007074:Immunoglobulin G; D007075:Immunoglobulin M