ArticleFrontiers in immunology2017
Different Somatic Hypermutation Levels among Antibody Subclasses Disclosed by a New Next-Generation Sequencing-Based Antibody Repertoire Analysis.
Article in Frontiers in immunology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 papers.
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Who cites it
77 citing papers in PubMed, 117 citations in OpenAlex.
- Evaluating southern pigtail macaques as an immunological model for human antibody responses.Scientific reports · 2026Article
- Transcriptome-Proteome Analysis of Human Naive and Memory B Cell Subsets Reveals Isotype and Subclass-Specific Phenotypes.European journal of immunology · 2026Article
- Characteristics of anti-integrin αvβ6 autoantibodies in patients with ulcerative colitis.JCI insight · 2026Article
- LM-QASAS: reference-free identification of antigen-specific sequences from the BCR repertoire using antibody language models.Frontiers in immunology · 2026Article
- Immunoglobulin germline reference sequences enable investigations and reveal insights into bat-specific immunity.iScience · 2025Article
- Humoral immunity after hematopoietic stem cell transplantation: evaluation by B-cell receptor repertoire analysis.International journal of hematology · 2025Article
- An iPSC-based in vitro model recapitulates human thymic epithelial development and multi-lineage specification.Nature communications · 2025Article
- Modeling of T cell-mediated autoimmune pituitary disease using human induced pluripotent stem cell-originated organoid.Nature communications · 2025Article
- Increased SARS-CoV-2 IgG4 has variable consequences dependent upon Fc function, Fc receptor polymorphism, and viral variant.Science advances · 2025Article
- Elimination of residual adult T-cell leukaemia clones by Tax-targeted dendritic cell vaccine.EJHaem · 2025Article
- Article
- Human interleukin-4-dependent facilitation of human IgG production in PBL-NOG-hIL-4-Tg mice.Frontiers in immunology · 2025Article
- Mice carrying the full-length human immunoglobulin loci produce antigen-specific human antibodies with the lambda light chain.iScience · 2024Article
- Immunomolecular and reactivity landscapes of gut IgA subclasses in homeostasis and inflammatory bowel disease.The Journal of experimental medicine · 2024Article
- Addressing the antibody germline bias and its effect on language models for improved antibody design.Bioinformatics (Oxford, England) · 2024Article
- Low-frequency CD8NPJ vaccines · 2024Article
- Immunoglobulin class-switch recombination: Mechanism, regulation, and related diseases.MedComm · 2024Review
- Analysis of B-cell receptor repertoire to evaluate immunogenicity of monovalent Omicron XBB.1.5 mRNA vaccines.EJHaem · 2024Article
- Qualitative Immunoglobulin Deficiency Causes Bacterial Infections in Patients with STAT1 Gain-of-Function Mutations.Journal of clinical immunology · 2024Article
- Single-cell immune repertoire analysis.Nature methods · 2024Review
17 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
A diverse antibody repertoire is primarily generated by the rearrangement of V, D, and J genes and subsequent somatic hypermutation (SHM). Class-switch recombination (CSR) produces various isotypes and subclasses with different functional properties. Although antibody isotypes and subclasses are considered to be produced by both direct and sequential CSR, it is still not fully understood how SHMs accumulate during the process in which antibody subclasses are generated. Here, we developed a new next-generation sequencing (NGS)-based antibody repertoire analysis capable of identifying all antibody isotype and subclass genes and used it to examine the peripheral blood mononuclear cells of 12 healthy individuals. Using a total of 5,480,040 sequences, we compared percentage frequency of variable (V), junctional (J) sequence, and a combination of V and J, diversity, length, and amino acid compositions of CDR3, SHM, and shared clones in the IgM, IgD, IgG3, IgG1, IgG2, IgG4, IgA1, IgE, and IgA2 genes. The usage and diversity were similar among the immunoglobulin (Ig) subclasses. Clonally related sequences sharing identical V, D, J, and CDR3 amino acid sequences were frequently found within multiple Ig subclasses, especially between IgG1 and IgG2 or IgA1 and IgA2. SHM occurred most frequently in IgG4, while IgG3 genes were the least mutated among all IgG subclasses. The shared clones had almost the same SHM levels among Ig subclasses, while subclass-specific clones had different levels of SHM dependent on the genomic location. Given the sequential CSR, these results suggest that CSR occurs sequentially over multiple subclasses in the order corresponding to the genomic location of IGHCs, but CSR is likely to occur more quickly than SHMs accumulate within Ig genes under physiological conditions. NGS-based antibody repertoire analysis should provide critical information on how various antibodies are generated in the immune system.
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