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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.

Publication ,  Journal Article
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 ...
Published in: PLoS One
2014

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.

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Published In

PLoS One

DOI

EISSN

1932-6203

Publication Date

2014

Volume

9

Issue

3

Start / End Page

e90725

Location

United States

Related Subject Headings

  • Treatment Outcome
  • Symbiosis
  • Sequence Alignment
  • Recombinant Proteins
  • Receptors, Antigen, B-Cell
  • Protein Binding
  • Paraproteins
  • Molecular Sequence Data
  • Leukemia, Lymphocytic, Chronic, B-Cell
  • Intestines
 

Citation

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Hwang, K.-K., Trama, A. M., Kozink, D. M., Chen, X., Wiehe, K., Cooper, A. J., … 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), e90725. https://doi.org/10.1371/journal.pone.0090725
Hwang, Kwan-Ki, Ashley M. Trama, Daniel M. Kozink, Xi Chen, Kevin Wiehe, Abby J. Cooper, Shi-Mao Xia, et al. “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, no. 3 (2014): e90725. https://doi.org/10.1371/journal.pone.0090725.
Hwang, Kwan-Ki, et al. “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, 2014, p. e90725. Pubmed, doi:10.1371/journal.pone.0090725.
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. 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. 2014;9(3):e90725.

Published In

PLoS One

DOI

EISSN

1932-6203

Publication Date

2014

Volume

9

Issue

3

Start / End Page

e90725

Location

United States

Related Subject Headings

  • Treatment Outcome
  • Symbiosis
  • Sequence Alignment
  • Recombinant Proteins
  • Receptors, Antigen, B-Cell
  • Protein Binding
  • Paraproteins
  • Molecular Sequence Data
  • Leukemia, Lymphocytic, Chronic, B-Cell
  • Intestines