ArticlePloS one2014
IGHV1-69 B cell chronic lymphocytic leukemia antibodies cross-react with HIV-1 and hepatitis C virus antigens as well as intestinal commensal bacteria.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 43 citations in OpenAlex.
- Influence of gut microbiota on chronic lymphocytic leukemia development and aggressiveness.Gut microbes reports · 2027Article
- Recurrent antibody repertoire features associated with six selected human IGHV genes: V(D)J usage, heavy-light pairing, and CDRH3 properties.Frontiers in immunology · 2026Article
- Framework-mediated binding of foreign and self-glycans by IGHV4-34 antibodies.Frontiers in immunology · 2026Review
- Conventional and non-conventional antigen-binding sites promote the development and function of chronic lymphocytic leukemia stereotyped subset #4 clones.Frontiers in immunology · 2025Article
- B cell receptor signaling and associated pathways in the pathogenesis of chronic lymphocytic leukemia.Frontiers in oncology · 2024Review
- Germline-encoded specificities and the predictability of the B cell response.PLoS pathogens · 2023Article
- Old and New Facts and Speculations on the Role of the B Cell Receptor in the Origin of Chronic Lymphocytic Leukemia.International journal of molecular sciences · 2022Review
- Novel CD81 Mutations in a Chinese Patient Led to IgA Nephropathy and Impaired BCR Signaling.Journal of clinical immunology · 2022Article
- The autoimmune signature of hyperinflammatory multisystem inflammatory syndrome in children.The Journal of clinical investigation · 2021Article
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- Engineering an Antibody V Gene-Selective Vaccine.Frontiers in immunology · 2021Article
- The Hydropathy Index of the HCDR3 Region of the B-Cell Receptor Identifies Two Subgroups of IGHV-Mutated Chronic Lymphocytic Leukemia Patients With Distinct Outcome.Frontiers in oncology · 2021Article
- Public Immunity: Evolutionary Spandrels for Pathway-Amplifying Protective Antibodies.Frontiers in immunology · 2021Review
- A Single Human VCell reports · 2020Article
- Mechanisms of B Cell Receptor Activation and Responses to B Cell Receptor Inhibitors in B Cell Malignancies.Cancers · 2020Review
- Analysis of the Targets and Glycosylation of Monoclonal IgAs From MGUS and Myeloma Patients.Frontiers in immunology · 2020Article
- Editorial: Structure, Isotypes, Targets, and Post-translational Modifications of Immunoglobulins and Their Role in Infection, Inflammation and Autoimmunity.Frontiers in immunology · 2020Article
- Polyreactive antibodies in CLL correlate with the level of immunoglobulins not the number of B lymphocytes.Leukemia & lymphoma · 2019Article
- The presence of CLL-associated stereotypic B cell receptors in the normal BCR repertoire from healthy individuals increases with age.Immunity & ageing : I & A · 2019Article
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Authors and funding
22 authors at 4 institutions in 2 countries.
Funding
Abstract
B-cell chronic lymphocytic leukemia (B-CLL) patients expressing unmutated immunoglobulin heavy variable regions (IGHVs) use the IGHV1-69 B cell receptor (BCR) in 25% of cases. Since HIV-1 envelope gp41 antibodies also frequently use IGHV1-69 gene segments, we hypothesized that IGHV1-69 B-CLL precursors may contribute to the gp41 B cell response during HIV-1 infection. To test this hypothesis, we rescued 5 IGHV1-69 unmutated antibodies as heterohybridoma IgM paraproteins and as recombinant IgG1 antibodies from B-CLL patients, determined their antigenic specificities and analyzed BCR sequences. IGHV1-69 B-CLL antibodies were enriched for reactivity with HIV-1 envelope gp41, influenza, hepatitis C virus E2 protein and intestinal commensal bacteria. These IGHV1-69 B-CLL antibodies preferentially used IGHD3 and IGHJ6 gene segments and had long heavy chain complementary determining region 3s (HCDR3s) (≥21 aa). IGHV1-69 B-CLL BCRs exhibited a phenylalanine at position 54 (F54) of the HCDR2 as do rare HIV-1 gp41 and influenza hemagglutinin stem neutralizing antibodies, while IGHV1-69 gp41 antibodies induced by HIV-1 infection predominantly used leucine (L54) allelic variants. These results demonstrate that the B-CLL cell population is an expansion of members of the innate polyreactive B cell repertoire with reactivity to a number of infectious agent antigens including intestinal commensal bacteria. The B-CLL IGHV1-69 B cell usage of F54 allelic variants strongly suggests that IGHV1-69 B-CLL gp41 antibodies derive from a restricted B cell pool that also produces rare HIV-1 gp41 and influenza hemagglutinin stem antibodies.
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