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- Title
<i>IGHV</i>1-69 B Cell Chronic Lymphocytic Leukemia Antibodies Cross-React with HIV-1 and Hepatitis C Virus Antigens as Well as Intestinal Commensal Bacteria.
- 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
- 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.
- Subjects
CHRONIC lymphocytic leukemia; B cell lymphoma; IMMUNOGLOBULINS; CROSS reactions (Immunology); HIV; HEPATITIS C virus; VIRAL antigens; GUT microbiome
- Publication
PLoS ONE, 2014, Vol 9, Issue 3, p1
- ISSN
1932-6203
- Publication type
Article
- DOI
10.1371/journal.pone.0090725