B-cell repertoire responses to varicella-zoster vaccination in human identical twins

Chen Wang, Yi Liu, Mary M. Cavanagh, Sab Le Saux, Qian Qi, Krishna M. Roskin, Timothy J. Looney, Ji Yeun Lee, Vaishali Dixit, Cornelia L. Dekker, Gary E. Swan, Jörg J. Goronzy, Scott D. Boyd

Research output: Contribution to journalArticlepeer-review

64 Scopus citations

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 varicellazoster 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 Bcell 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.

Original languageEnglish (US)
Pages (from-to)500-505
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume112
Issue number2
DOIs
StatePublished - Jan 13 2015

Keywords

  • Antibody
  • B cell repertoire
  • Convergent
  • Twin
  • Varicella zoster vaccine

ASJC Scopus subject areas

  • General

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