IGHV1-69 polymorphism modulates anti-influenza antibody repertoires, correlates with IGHV utilization shifts and varies by ethnicity

Yuval Avnir, Corey T. Watson, Jacob Glanville, Eric C. Peterson, Aimee S. Tallarico, Andrew S. Bennett, Kun Qin, Ying Fu, Chiung Yu Huang, John H. Beigel, Felix Breden, Quan Zhu, Wayne A. Marasco

Research output: Contribution to journalArticlepeer-review

Abstract

IGHV polymorphism provides a rich source of humoral immune system diversity. One important example is the IGHV1-69 germline gene where the biased use of alleles that encode the critical CDR-H2 Phe54 (F-alleles) to make broadly neutralizing antibodies (HV1-69-sBnAb) to the influenza A hemagglutinin stem domain has been clearly established. However, whether IGHV1-69 polymorphism can also modulate B cell function and Ab repertoire expression through promoter and copy number (CN) variations has not been reported, nor has whether IGHV1-69 allelic distribution is impacted by ethnicity. Here we studied a cohort of NIH H5N1 vaccinees and demonstrate for the first time the influence of IGHV1-69 polymorphism on V-segment usage, somatic hypermutation and B cell expansion that elucidates the dominance of F-alleles in HV1-69-sBnAbs. We provide evidence that Phe54/Leu54 (F/L) polymorphism correlates with shifted repertoire usage of other IGHV germline genes. In addition, we analyzed ethnically diverse individuals within the 1000 genomes project and discovered marked variations in F-and L-genotypes and CN among the various ethnic groups that may impact HV1-69-sBnAb responses. These results have immediate implications for understanding HV1-69-sBnAb responses at the individual and population level and for the design and implementation of 'universal influenza vaccine.

Original languageEnglish (US)
Article number20842
JournalScientific reports
Volume6
DOIs
StatePublished - Feb 16 2016

ASJC Scopus subject areas

  • General

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