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

Kwan-Ki Hwang; Ashley M Trama; Daniel M Kozink; Xi Chen; Kevin Wiehe; Abby J Cooper; Shi-Mao Xia; Minyue Wang; Dawn J Marshall; John Whitesides; Munir Alam; Georgia D Tomaras; Steven L Allen; Kanti R Rai; Jane McKeating; Rosa Catera; Xiao-Jie Yan; Charles C Chu; Garnett Kelsoe; Hua-Xin Liao; Nicholas Chiorazzi; Barton F Haynes

doi:10.1371/journal.pone.0090725

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

Kwan-Ki Hwang, Ashley M Trama, Daniel M Kozink, Xi Chen, Kevin Wiehe, Abby J Cooper, Shi-Mao Xia, Minyue Wang, Dawn J Marshall, John Whitesides, Munir Alam, Georgia D Tomaras, Steven L Allen, Kanti R Rai, Jane McKeating, Rosa Catera, Xiao-Jie Yan, Charles C Chu, Garnett Kelsoe, Hua-Xin LiaoNicholas Chiorazzi, Barton F Haynes

Immunology and Immunotherapy

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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.

Original language	English
Article number	e90725
Number of pages	9
Journal	PLoS ONE
Volume	9
Issue number	3
DOIs	https://doi.org/10.1371/journal.pone.0090725
Publication status	Published - 10 Mar 2014

Keywords

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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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https://doi.org/10.1371/journal.pone.0090725Licence: Creative Commons: Attribution (CC BY)

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Hwang, K-K., Trama, A. M., Kozink, D. M., Chen, X., Wiehe, K., Cooper, A. J., Xia, S-M., Wang, M., Marshall, D. J., Whitesides, J., Alam, M., Tomaras, G. D., Allen, S. L., Rai, K. R., McKeating, J., Catera, R., Yan, X-J., Chu, C. C., Kelsoe, G., ... Haynes, B. 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), Article e90725. https://doi.org/10.1371/journal.pone.0090725

@article{9705123983e5440bbf869e8863dc28a9,

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",

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.",

keywords = "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",

author = "Kwan-Ki Hwang and Trama, {Ashley M} and Kozink, {Daniel M} and Xi Chen and Kevin Wiehe and Cooper, {Abby J} and Shi-Mao Xia and Minyue Wang and Marshall, {Dawn J} and John Whitesides and Munir Alam and Tomaras, {Georgia D} and Allen, {Steven L} and Rai, {Kanti R} and Jane McKeating and Rosa Catera and Xiao-Jie Yan and Chu, {Charles C} and Garnett Kelsoe and Hua-Xin Liao and Nicholas Chiorazzi and Haynes, {Barton F}",

year = "2014",

month = mar,

day = "10",

doi = "10.1371/journal.pone.0090725",

language = "English",

volume = "9",

journal = "PLoS ONE",

issn = "1932-6203",

publisher = "Public Library of Science (PLOS)",

number = "3",

}

Hwang, K-K, Trama, AM, Kozink, DM, Chen, X, Wiehe, K, Cooper, AJ, Xia, S-M, Wang, M, Marshall, DJ, Whitesides, J, Alam, M, Tomaras, GD, Allen, SL, Rai, KR, McKeating, J, Catera, R, Yan, X-J, Chu, CC, Kelsoe, G, Liao, H-X, Chiorazzi, N & Haynes, BF 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, vol. 9, no. 3, e90725. https://doi.org/10.1371/journal.pone.0090725

TY - JOUR

T1 - IGHV1-69 B cell chronic lymphocytic leukemia antibodies cross-react with HIV-1 and hepatitis C virus antigens as well as intestinal commensal bacteria

AU - Hwang, Kwan-Ki

AU - Trama, Ashley M

AU - Kozink, Daniel M

AU - Chen, Xi

AU - Wiehe, Kevin

AU - Cooper, Abby J

AU - Xia, Shi-Mao

AU - Wang, Minyue

AU - Marshall, Dawn J

AU - Whitesides, John

AU - Alam, Munir

AU - Tomaras, Georgia D

AU - Allen, Steven L

AU - Rai, Kanti R

AU - McKeating, Jane

AU - Catera, Rosa

AU - Yan, Xiao-Jie

AU - Chu, Charles C

AU - Kelsoe, Garnett

AU - Liao, Hua-Xin

AU - Chiorazzi, Nicholas

AU - Haynes, Barton F

PY - 2014/3/10

Y1 - 2014/3/10

N2 - 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.

AB - 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.

KW - Alleles

KW - Amino Acid Sequence

KW - Antibodies, Monoclonal

KW - Antibodies, Neoplasm

KW - Bacteria

KW - Cell Line, Tumor

KW - Cross Reactions

KW - HIV Antigens

KW - HIV Infections

KW - HIV-1

KW - Hepacivirus

KW - Hepatitis C Antigens

KW - Humans

KW - Hybridomas

KW - Immunoglobulin Heavy Chains

KW - Immunoglobulin Variable Region

KW - Intestines

KW - Leukemia, Lymphocytic, Chronic, B-Cell

KW - Molecular Sequence Data

KW - Paraproteins

KW - Protein Binding

KW - Receptors, Antigen, B-Cell

KW - Recombinant Proteins

KW - Sequence Alignment

KW - Symbiosis

KW - Treatment Outcome

U2 - 10.1371/journal.pone.0090725

DO - 10.1371/journal.pone.0090725

M3 - Article

C2 - 24614505

SN - 1932-6203

VL - 9

JO - PLoS ONE

JF - PLoS ONE

IS - 3

M1 - e90725

ER -

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

Keywords

UN SDGs

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