IGHV1-69 B cell chronic lymphocytic leukemia antibodies cross-react with HIV-1 and hepatitis C virus antigens as well as intestinal commensal bacteria.
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 articleSubject
AllelesAmino 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
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https://hdl.handle.net/10161/10901Published Version (Please cite this version)
10.1371/journal.pone.0090725Publication 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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Show full item recordScholars@Duke
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
Barton Ford Haynes
Frederic M. Hanes Distinguished Professor of Medicine
Barton F. Haynes, M.D. is the Frederic M. Hanes Professor of Medicine and Immunology,
and Director of the Duke Human Vaccine Institute. Prior to leading the DHVI, Dr. Haynes
served as Chief of the Division of Rheumatology, Allergy and Clinical Immunology,
and later as Chair of the Department of Medicine. As Director of the Duke Human Vaccine
Institute, Bart Haynes is leading a team of investigators working on vaccines for
emerging infections, including tuberculosis, pandemic influenza, emergi
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,
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
This author no longer has a Scholars@Duke profile, so the information shown here reflects
their Duke status at the time this item was deposited.
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
Kevin J Wiehe
Norman L. Letvin Associate Professor in Medicine
Dr. Kevin Wiehe is the associate director of research, director of computational biology
and co-director of the Quantitative Research Division at the Duke Human Vaccine Institute
(DHVI). He has over 20 years of experience in the field of computational biology and
has expertise in computational structural biology, computational genomics, and computational
immunology.
For the past decade, he has applied his unique background to developing computational
approaches for studying the B cell
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