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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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.
Amino Acid Sequence
Cell Line, Tumor
Hepatitis C Antigens
Immunoglobulin Heavy Chains
Immunoglobulin Variable Region
Leukemia, Lymphocytic, Chronic, B-Cell
Molecular Sequence Data
Receptors, Antigen, B-Cell
Published Version (Please cite this version)10.1371/journal.pone.0090725
Publication InfoHwang, 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.
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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
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
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,
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
Professor in Surgery
Research in the Tomaras Laboratory in the Duke Human Vaccine Institute and Departments of Surgery, Immunology, and Molecular Genetics and Microbiology at Duke University Medical Center, focuses on the identification of immune correlates of protection for preventative vaccines and identification of the mechanisms responsible for potent inhibition of human pathogens.
Assistant Professor in Medicine
Associate Professor in Medicine
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