IGHV1-69-encoded antibodies expressed in chronic lymphocytic leukemia react with malondialdehyde-acetaldehyde adduct, an immunodominant oxidation-specific epitope.
The immunoglobulins expressed by chronic lymphocytic leukemia (CLL) B cells are highly restricted, suggesting they are selected for binding either self or foreign antigen. Of the immunoglobulin heavy-chain variable (IGHV) genes expressed in CLL, IGHV1-69 is the most common, and often is expressed wi...
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doaj-cc98243a866544aaaf1436e650601acd2020-11-25T02:31:24ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0186e6520310.1371/journal.pone.0065203IGHV1-69-encoded antibodies expressed in chronic lymphocytic leukemia react with malondialdehyde-acetaldehyde adduct, an immunodominant oxidation-specific epitope.Xuchu QueGeorge F WidhopfShahzada AmirKarsten HartvigsenLotte F HansenDouglas WoelkersSotirios TsimikasChristoph J BinderThomas J KippsJoseph L WitztumThe immunoglobulins expressed by chronic lymphocytic leukemia (CLL) B cells are highly restricted, suggesting they are selected for binding either self or foreign antigen. Of the immunoglobulin heavy-chain variable (IGHV) genes expressed in CLL, IGHV1-69 is the most common, and often is expressed with little or no somatic mutation, and restricted IGHD and IGHJ gene usage. We found that antibodies encoded by one particular IGHV1-69 subset, designated CLL69C, with the HCDR3 encoded by the IGHD3-3 gene in reading frame 2 and IGHJ6, specifically bound to oxidation-specific epitopes (OSE), which are products of enhanced lipid peroxidation and a major target of innate natural antibodies. Specifically, CLL69C bound immunodominant OSE adducts termed MAA (malondialdehyde-acetaldehyde-adducts), which are found on apoptotic cells, inflammatory tissues, and atherosclerotic lesions. It also reacted specifically with MAA-specific peptide mimotopes. Light chain shuffling indicated that non-stochastically paired L chain of IGLV3-9 contributes to the antigen binding of CLL69C. A nearly identical CLL69C Ig heavy chain was identified from an MAA-enriched umbilical cord phage displayed Fab library, and a derived Fab with the same HCDR3 rearrangement displayed identical MAA-binding properties. These data support the concept that OSE (MAA-epitopes), which are ubiquitous products of inflammation, may play a role in clonal selection and expansion of CLL B cells.http://europepmc.org/articles/PMC3688726?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Xuchu Que George F Widhopf Shahzada Amir Karsten Hartvigsen Lotte F Hansen Douglas Woelkers Sotirios Tsimikas Christoph J Binder Thomas J Kipps Joseph L Witztum |
spellingShingle |
Xuchu Que George F Widhopf Shahzada Amir Karsten Hartvigsen Lotte F Hansen Douglas Woelkers Sotirios Tsimikas Christoph J Binder Thomas J Kipps Joseph L Witztum IGHV1-69-encoded antibodies expressed in chronic lymphocytic leukemia react with malondialdehyde-acetaldehyde adduct, an immunodominant oxidation-specific epitope. PLoS ONE |
author_facet |
Xuchu Que George F Widhopf Shahzada Amir Karsten Hartvigsen Lotte F Hansen Douglas Woelkers Sotirios Tsimikas Christoph J Binder Thomas J Kipps Joseph L Witztum |
author_sort |
Xuchu Que |
title |
IGHV1-69-encoded antibodies expressed in chronic lymphocytic leukemia react with malondialdehyde-acetaldehyde adduct, an immunodominant oxidation-specific epitope. |
title_short |
IGHV1-69-encoded antibodies expressed in chronic lymphocytic leukemia react with malondialdehyde-acetaldehyde adduct, an immunodominant oxidation-specific epitope. |
title_full |
IGHV1-69-encoded antibodies expressed in chronic lymphocytic leukemia react with malondialdehyde-acetaldehyde adduct, an immunodominant oxidation-specific epitope. |
title_fullStr |
IGHV1-69-encoded antibodies expressed in chronic lymphocytic leukemia react with malondialdehyde-acetaldehyde adduct, an immunodominant oxidation-specific epitope. |
title_full_unstemmed |
IGHV1-69-encoded antibodies expressed in chronic lymphocytic leukemia react with malondialdehyde-acetaldehyde adduct, an immunodominant oxidation-specific epitope. |
title_sort |
ighv1-69-encoded antibodies expressed in chronic lymphocytic leukemia react with malondialdehyde-acetaldehyde adduct, an immunodominant oxidation-specific epitope. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2013-01-01 |
description |
The immunoglobulins expressed by chronic lymphocytic leukemia (CLL) B cells are highly restricted, suggesting they are selected for binding either self or foreign antigen. Of the immunoglobulin heavy-chain variable (IGHV) genes expressed in CLL, IGHV1-69 is the most common, and often is expressed with little or no somatic mutation, and restricted IGHD and IGHJ gene usage. We found that antibodies encoded by one particular IGHV1-69 subset, designated CLL69C, with the HCDR3 encoded by the IGHD3-3 gene in reading frame 2 and IGHJ6, specifically bound to oxidation-specific epitopes (OSE), which are products of enhanced lipid peroxidation and a major target of innate natural antibodies. Specifically, CLL69C bound immunodominant OSE adducts termed MAA (malondialdehyde-acetaldehyde-adducts), which are found on apoptotic cells, inflammatory tissues, and atherosclerotic lesions. It also reacted specifically with MAA-specific peptide mimotopes. Light chain shuffling indicated that non-stochastically paired L chain of IGLV3-9 contributes to the antigen binding of CLL69C. A nearly identical CLL69C Ig heavy chain was identified from an MAA-enriched umbilical cord phage displayed Fab library, and a derived Fab with the same HCDR3 rearrangement displayed identical MAA-binding properties. These data support the concept that OSE (MAA-epitopes), which are ubiquitous products of inflammation, may play a role in clonal selection and expansion of CLL B cells. |
url |
http://europepmc.org/articles/PMC3688726?pdf=render |
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