2026-03-26 カロリンスカ研究所（KI）
Researchers have investigated how genetic differences affect the immune response to the influenza virus. Photo: Getty Images
＜関連情報＞
- https://news.ki.se/large-mapping-of-hereditary-differences-in-the-immune-system
- https://www.cell.com/immunity/fulltext/S1074-7613(26)00113-5
- https://www.cell.com/immunity/fulltext/S1074-7613(26)00047-6
遺伝的に多様なインフルエンザ抗体は、免疫グロブリン生殖細胞系遺伝子変異の役割を浮き彫りにし、集団全体を対象としたワクチン戦略に役立つ Genetically diverse influenza antibodies highlight the role of IG germline gene variation and inform population-comprehensive vaccine strategies
Alexandra A. Fischer, ∙ Martin Corcoran ∙ Philip J.M. Brouwer ∙ … ∙ Andrew B. Ward ∙ Julianna Han ∙ Gunilla B. Karlsson Hedestam
Immunity Published:March 26, 2026
DOI:https://doi.org/10.1016/j.immuni.2026.03.002
Highlights
- Extensive inter-individual differences in influenza HA-specific Ab responses
- ISCAPE uncovers B cell polyclonality and allele-dependent functionality
- A common polymorphism in IGHV2-70 dictates LPAF-a-class Ab elicitation
- Genetically diverse central stem-targeting bNAbs were structurally defined
Summary
The regular emergence of influenza strains with pandemic potential necessitates vaccines that elicit protective immune responses across genetically diverse human populations. A critical but understudied factor is how germline-encoded variation in immunoglobulin genes shapes the development of neutralizing antibodies. Here, by combining personalized immunoglobulin genotyping with high-throughput paired-chain antibody sequencing from influenza A hemagglutinin (HA)-binding B cells across four donors, using a technique we developed called individualized single-cell analysis of paired expressed antigen receptors (ISCAPE), we demonstrate that B cell responses to HA are highly individual. We identified a common IGHV2-70 polymorphism that impaired the function of a class of neutralizing HA head-directed antibodies. Furthermore, we described HA central stem-targeting broadly neutralizing antibodies that utilize IGHD3-3 recombined with diverse IGHV genes, expanding the known repertoire of stem antibodies and highlighting antibody gene usage population restrictions. We suggest that multi-donor repertoire studies, coupled with personalized immunoglobulin genotyping, can uncover germline-encoded functional variations and help mitigate population vulnerabilities in vaccine design.
25のグローバル集団を対象とした超高スループットIGH遺伝子型解析により、集団に偏った対立遺伝子多様性とホモ接合型VおよびD遺伝子欠失が明らかになった Ultra-high-throughput IGH genotyping of 25 global populations reveals population-biased allelic diversity and homozygous V and D gene deletions
Martin Corcoran ∙ Sanjana Narang ∙ Mateusz Kaduk ∙ … ∙ Anna Färnert,, ∙ Christopher Sundling ∙ Gunilla B. Karlsson Hedestam
Immunity Published:March 16, 2026
DOI:https://doi.org/10.1016/j.immuni.2026.01.026
Highlights
- Population frequencies of 561 IGHV alleles identified in 25 global human populations
- A homozygous deletion of six IGHD genes was present in up to 30% of East Asians
- Population-biased variations found in IG genes frequently used in pathogen responses
- Meiotic recombination alterations were shown to maintain IGH locus heterogeneity
Summary
The extraordinary diversity of human immunoglobulin (IG) genes underpins effective antibody responses, yet the full scope and functional impact of germline-encoded IG variation across populations is largely unknown. Here, we present ImmuneDiscover, an ultra-high-throughput sequencing platform enabling individualized IG genotyping from nanogram-scale DNA and simultaneous analysis of over 1,000 individuals. Using ImmuneDiscover, we generated high-resolution IG genotypes for 2,486 individuals from the 1,000 Genomes Project, spanning diverse population ancestries, and built Karolinska Institutet Adaptive Immune Receptor Gene Variant Atlas (KIARVA), an open access atlas of IG gene variation. Cross-validation with single-nucleotide polymorphism data from over one million genomes confirmed the accuracy of discovered alleles. Our analysis reveals population-specific patterns, including a multigene IG heavy-chain diversity (IGHD) deletion found homozygously in up to 30% of East Asian individuals, and haplotypic differences linked to disease-associated loci. These findings illuminate the evolutionary forces shaping IG gene diversity and provide a foundational resource for investigating the immunogenetic basis of pathogen susceptibility and vaccine responsiveness worldwide.
