title: B-cell repertoire responses to varicella-zoster vaccination in human identical twins.
abstract: Adaptive immune responses in humans rely on somatic genetic rearrangements of Ig and T-cell receptor loci to generate diverse antigen receptors. It is unclear to what extent an individual's genetic background affects the characteristics of the antibody repertoire used in responding to vaccination or infection. We studied the B-cell repertoires and clonal expansions in response to attenuated varicella-zoster vaccination in four pairs of adult identical twins and found that the global antibody repertoires of twin pair members showed high similarity in antibody heavy chain V, D, and J gene segment use, and in the length and features of the complementarity-determining region 3, a major determinant of antigen binding. These twin similarities were most pronounced in the IgM-expressing B-cell pools, but were seen to a lesser extent in IgG-expressing B cells. In addition, the degree of antibody somatic mutation accumulated in the B-cell repertoire was highly correlated within twin pair members. Twin pair members had greater numbers of shared convergent antibody sequences, including mutated sequences, suggesting similarity among memory B-cell clonal lineages. Despite these similarities in the memory repertoire, the B-cell clones used in acute responses to ZOSTAVAX vaccination were largely unique to each individual. Taken together, these results suggest that the overall B-cell repertoire is significantly shaped by the underlying germ-line genome, but that stochastic or individual-specific effects dominate the selection of clones in response to an acute antigenic stimulus.
authors.affiliation: Department of Pathology.
authors.forename: Chen
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Pathology, Biomedical Informatics Training Program.
authors.forename: Yi
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Division of Immunology and Rheumatology, Department of Medicine.
authors.forename: Mary M
authors.initials: MM
authors.lastname: Cavanagh
authors.affiliation: Division of Immunology and Rheumatology, Department of Medicine.
authors.forename: Sabine
authors.initials: S
authors.lastname: Le Saux
authors.affiliation: Division of Immunology and Rheumatology, Department of Medicine.
authors.forename: Qian
authors.initials: Q
authors.lastname: Qi
authors.affiliation: Department of Pathology.
authors.forename: Krishna M
authors.initials: KM
authors.lastname: Roskin
authors.affiliation: Department of Pathology.
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Looney
authors.affiliation: Department of Pathology.
authors.forename: Ji-Yeun
authors.initials: JY
authors.lastname: Lee
authors.affiliation: Department of Pathology.
authors.forename: Vaishali
authors.initials: V
authors.lastname: Dixit
authors.affiliation: Department of Pediatrics, and.
authors.forename: Cornelia L
authors.initials: CL
authors.lastname: Dekker
authors.affiliation: Stanford Prevention Research Center, Stanford University, Stanford, CA 94305; and.
authors.forename: Gary E
authors.initials: GE
authors.lastname: Swan
authors.affiliation: Division of Immunology and Rheumatology, Department of Medicine, Department of Medicine, Veterans Affairs Palo Alto Health Care System, Palo Alto, CA 94304.
authors.forename: Jörg J
authors.initials: JJ
authors.lastname: Goronzy
authors.affiliation: Department of Pathology, sboyd1@stanford.edu.
authors.forename: Scott D
authors.initials: SD
authors.lastname: Boyd
mesh_terms: D000914:Antibodies, Viral / Q000096:biosynthesis* / Q000235:genetics*; D001402:B-Lymphocytes / Q000276:immunology*; D015331:Cohort Studies; D022801:Complementarity Determining Regions / Q000235:genetics; D005260:Female; D053061:Herpes Zoster Vaccine / Q000276:immunology*; D014645:Herpesvirus 3, Human / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000235:genetics; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007075:Immunoglobulin M / Q000235:genetics; D007156:Immunologic Memory / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation; D014430:Twins, Monozygotic / Q000235:genetics*
chemical_list: D000914:Antibodies, Viral; D022801:Complementarity Determining Regions; D053061:Herpes Zoster Vaccine; D007074:Immunoglobulin G; D007143:Immunoglobulin Heavy Chains; D007075:Immunoglobulin M
keywords: B cell repertoire; Varicella Zoster vaccine; antibody; convergent; twin