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IGHV1-69 B cell chronic lymphocytic leukemia antibodies cross-react with HIV-1 and hepatitis C virus antigens as well as intestinal commensal bacteria.

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Date
2014
Authors
Hwang, Kwan-Ki
Trama, Ashley M
Kozink, Daniel M
Chen, Xi
Wiehe, Kevin
Cooper, Abby J
Xia, Shi-Mao
Wang, Minyue
Marshall, Dawn J
Whitesides, John
Alam, Munir
Tomaras, Georgia D
Allen, Steven L
Rai, Kanti R
McKeating, Jane
Catera, Rosa
Yan, Xiao-Jie
Chu, Charles C
Kelsoe, Garnett
Liao, Hua-Xin
Chiorazzi, Nicholas
Haynes, Barton F
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(22 total)
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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.
Type
Journal article
Subject
Alleles
Amino Acid Sequence
Antibodies, Monoclonal
Antibodies, Neoplasm
Bacteria
Cell Line, Tumor
Cross Reactions
HIV Antigens
HIV Infections
HIV-1
Hepacivirus
Hepatitis C Antigens
Humans
Hybridomas
Immunoglobulin Heavy Chains
Immunoglobulin Variable Region
Intestines
Leukemia, Lymphocytic, Chronic, B-Cell
Molecular Sequence Data
Paraproteins
Protein Binding
Receptors, Antigen, B-Cell
Recombinant Proteins
Sequence Alignment
Symbiosis
Treatment Outcome
Permalink
https://hdl.handle.net/10161/10901
Published Version (Please cite this version)
10.1371/journal.pone.0090725
Publication Info
Hwang, Kwan-Ki; Trama, Ashley M; Kozink, Daniel M; Chen, Xi; Wiehe, Kevin; Cooper, Abby J; ... Haynes, Barton F (2014). IGHV1-69 B cell chronic lymphocytic leukemia antibodies cross-react with HIV-1 and hepatitis C virus antigens as well as intestinal commensal bacteria. PLoS One, 9(3). pp. e90725. 10.1371/journal.pone.0090725. Retrieved from https://hdl.handle.net/10161/10901.
This is constructed from limited available data and may be imprecise. To cite this article, please review & use the official citation provided by the journal.
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Scholars@Duke

Alam

S. Munir Alam

Professor in Medicine
Research Interests.  The Alam laboratory’s primary research is focused on understanding the biophysical properties of antigen-antibody binding and the molecular events of early B cell activation using the HIV-1 broadly neutralizing antibody (bnAb) lineage models. We are studying how HIV-1 Envelope proteins of varying affinities are sensed by B cells expressing HIV-1 bnAbs or their germline antigen receptors and initiate early signaling events for their activation. In the lon
Haynes

Barton Ford Haynes

Frederic M. Hanes Distinguished Professor of Medicine
The Haynes lab is studying host innate and adaptive immune responses to the human immunodeficiency virus (HIV), tuberculosis (TB), and influenza in order to find the enabling technology to make preventive vaccines against these three major infectious diseases. Mucosal Immune Responses in Acute HIV Infection The Haynes lab is working to determine why broadly neutralizing antibodies are rarely made in acute HIV infection (AHI), currently a major obstacle in the de
Kelsoe

Garnett H. Kelsoe

James B. Duke Distinguished Professor of Immunology
1. Lymphocyte development and antigen-driven diversification of immunoglobulin and T cell antigen receptor genes. 2. The germinal center reaction and mechanisms for clonal selection and self - tolerance. The origins of autoimmunity. 3. Interaction of innate- and adaptive immunity and the role of inflammation in lymphoid organogenesis. 4. The role of secondary V(D)J gene rearrangment in lymphocyte development and malignancies. 5. Mathematical modeling of immune responses,
Liao

Hua-Xin Liao

Adjunct Professor in the Department of Medicine
Dr. Liao is a Professor of Medicine and Research Director of Duke Human Vaccine Institute. Dr. Liao is a MD virologistt rained in China. In early 1980’s, Dr. Liao made major contributions to the first isolation of epidemic hemorrhagic fever virus (hataanvirus) from Apodemus agraius using tissue culture in China. The successful identification and isolation of Hataanvirus enabled the early diagnosis and treatment of the disease, and advancement of HFRS research towards prevention by de
Tomaras

Georgia Doris Tomaras

Professor in Surgery
Dr. Georgia Tomaras is a tenured Professor of Surgery, Professor of Immunology, Professor of Molecular Genetics and Microbiology and is a Fellow of the American Academy of Microbiology (AAM) and a Fellow of the American Association for the Advancement of Science (AAAS).  Dr. Tomaras is Co-Director of the Center for Human Systems Immunology (CHSI) Duke University and Director of the Duke Center for AIDS Research (CFAR). Her national and international leadership roles i

John Franklin Whitesides

Assistant Professor in Medicine
Wiehe

Kevin J Wiehe

Associate Professor in Medicine
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