IGHV1-69 B cell chronic lymphocytic leukemia antibodies cross-react with HIV-1 and hepatitis C virus antigens as well as intestinal commensal bacteria.
dc.contributor.author | Hwang, Kwan-Ki | |
dc.contributor.author | Trama, Ashley M | |
dc.contributor.author | Kozink, Daniel M | |
dc.contributor.author | Chen, Xi | |
dc.contributor.author | Wiehe, Kevin | |
dc.contributor.author | Cooper, Abby J | |
dc.contributor.author | Xia, Shi-Mao | |
dc.contributor.author | Wang, Minyue | |
dc.contributor.author | Marshall, Dawn J | |
dc.contributor.author | Whitesides, John | |
dc.contributor.author | Alam, Munir | |
dc.contributor.author | Tomaras, Georgia D | |
dc.contributor.author | Allen, Steven L | |
dc.contributor.author | Rai, Kanti R | |
dc.contributor.author | McKeating, Jane | |
dc.contributor.author | Catera, Rosa | |
dc.contributor.author | Yan, Xiao-Jie | |
dc.contributor.author | Chu, Charles C | |
dc.contributor.author | Kelsoe, Garnett | |
dc.contributor.author | Liao, Hua-Xin | |
dc.contributor.author | Chiorazzi, Nicholas | |
dc.contributor.author | Haynes, Barton F | |
dc.contributor.editor | Lu, Shan | |
dc.coverage.spatial | United States | |
dc.date.accessioned | 2015-11-18T16:37:20Z | |
dc.date.issued | 2014 | |
dc.description.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. | |
dc.identifier | ||
dc.identifier | PONE-D-13-43478 | |
dc.identifier.eissn | 1932-6203 | |
dc.identifier.uri | ||
dc.language | eng | |
dc.publisher | Public Library of Science (PLoS) | |
dc.relation.ispartof | PLoS One | |
dc.relation.isversionof | 10.1371/journal.pone.0090725 | |
dc.subject | Alleles | |
dc.subject | Amino Acid Sequence | |
dc.subject | Antibodies, Monoclonal | |
dc.subject | Antibodies, Neoplasm | |
dc.subject | Bacteria | |
dc.subject | Cell Line, Tumor | |
dc.subject | Cross Reactions | |
dc.subject | HIV Antigens | |
dc.subject | HIV Infections | |
dc.subject | HIV-1 | |
dc.subject | Hepacivirus | |
dc.subject | Hepatitis C Antigens | |
dc.subject | Humans | |
dc.subject | Hybridomas | |
dc.subject | Immunoglobulin Heavy Chains | |
dc.subject | Immunoglobulin Variable Region | |
dc.subject | Intestines | |
dc.subject | Leukemia, Lymphocytic, Chronic, B-Cell | |
dc.subject | Molecular Sequence Data | |
dc.subject | Paraproteins | |
dc.subject | Protein Binding | |
dc.subject | Receptors, Antigen, B-Cell | |
dc.subject | Recombinant Proteins | |
dc.subject | Sequence Alignment | |
dc.subject | Symbiosis | |
dc.subject | Treatment Outcome | |
dc.title | IGHV1-69 B cell chronic lymphocytic leukemia antibodies cross-react with HIV-1 and hepatitis C virus antigens as well as intestinal commensal bacteria. | |
dc.type | Journal article | |
duke.contributor.orcid | Alam, Munir|0000-0003-0941-0703 | |
duke.contributor.orcid | Tomaras, Georgia D|0000-0001-8076-1931 | |
duke.contributor.orcid | Kelsoe, Garnett|0000-0002-8770-040X | |
pubs.author-url | ||
pubs.begin-page | e90725 | |
pubs.issue | 3 | |
pubs.organisational-group | Basic Science Departments | |
pubs.organisational-group | Clinical Science Departments | |
pubs.organisational-group | Duke | |
pubs.organisational-group | Duke Cancer Institute | |
pubs.organisational-group | Duke Human Vaccine Institute | |
pubs.organisational-group | Global Health Institute | |
pubs.organisational-group | Immunology | |
pubs.organisational-group | Institutes and Centers | |
pubs.organisational-group | Institutes and Provost's Academic Units | |
pubs.organisational-group | Medicine | |
pubs.organisational-group | Medicine, Duke Human Vaccine Institute | |
pubs.organisational-group | Molecular Genetics and Microbiology | |
pubs.organisational-group | Pathology | |
pubs.organisational-group | School of Medicine | |
pubs.organisational-group | Surgery | |
pubs.organisational-group | Surgery, Surgical Sciences | |
pubs.organisational-group | University Institutes and Centers | |
pubs.publication-status | Published online | |
pubs.volume | 9 |
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