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

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Trama, Ashley M

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Kozink, Daniel M

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Chen, Xi

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Wiehe, Kevin

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Cooper, Abby J

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Xia, Shi-Mao

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Wang, Minyue

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Marshall, Dawn J

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Whitesides, John

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Alam, Munir

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Tomaras, Georgia D

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Allen, Steven L

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Rai, Kanti R

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McKeating, Jane

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Catera, Rosa

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Yan, Xiao-Jie

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Chu, Charles C

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Kelsoe, Garnett

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Liao, Hua-Xin

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Chiorazzi, Nicholas

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Haynes, Barton F

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Lu, Shan

dc.coverage.spatial

United States

dc.date.accessioned

2015-11-18T16:37:20Z

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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

http://www.ncbi.nlm.nih.gov/pubmed/24614505

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PONE-D-13-43478

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1932-6203

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https://hdl.handle.net/10161/10901

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eng

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Public Library of Science (PLoS)

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PLoS One

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10.1371/journal.pone.0090725

dc.subject

Alleles

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Amino Acid Sequence

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Antibodies, Monoclonal

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Antibodies, Neoplasm

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Bacteria

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Cell Line, Tumor

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Cross Reactions

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HIV Antigens

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HIV Infections

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HIV-1

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Hepacivirus

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Hepatitis C Antigens

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Humans

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Hybridomas

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Immunoglobulin Heavy Chains

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Immunoglobulin Variable Region

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Intestines

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Leukemia, Lymphocytic, Chronic, B-Cell

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Molecular Sequence Data

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Paraproteins

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Protein Binding

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Receptors, Antigen, B-Cell

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Recombinant Proteins

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Sequence Alignment

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Symbiosis

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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

http://www.ncbi.nlm.nih.gov/pubmed/24614505

pubs.begin-page

e90725

pubs.issue

3

pubs.organisational-group

Basic Science Departments

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Clinical Science Departments

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Duke

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Duke Cancer Institute

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Duke Human Vaccine Institute

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Global Health Institute

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Immunology

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Institutes and Centers

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Institutes and Provost's Academic Units

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Medicine

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Medicine, Duke Human Vaccine Institute

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Molecular Genetics and Microbiology

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Pathology

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School of Medicine

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Surgery

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Surgery, Surgical Sciences

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University Institutes and Centers

pubs.publication-status

Published online

pubs.volume

9

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