Format

Send to

Choose Destination
Sci Rep. 2016 Feb 16;6:20842. doi: 10.1038/srep20842.

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

Author information

1
Department of Cancer Immunology &AIDS, Dana-Farber Cancer Institute; Department of Medicine, Harvard Medical School, 450 Brookline Avenue, Boston, Massachusetts 02215, USA.
2
Department of Biological Sciences, Simon Fraser University, Burnaby, British Columbia, V5A 1S6, Canada.
3
Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
4
Program in Computational and Systems Immunology, Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, California, USA.
5
Division of Biostatistics and Bioinformatics Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University 550 N. Broadway, Room 1103-A Baltimore, Maryland 21205-2013, USA.
6
Leidos Biomedical Research Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21702 USA.

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.

PMID:
26880249
PMCID:
PMC4754645
DOI:
10.1038/srep20842
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center