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Selection of Apoptotic Cell Specific Human Antibodies from Adult Bone Marrow

Autoreactive antibodies that recognize neo-determinants on apoptotic cells in mice have been proposed to have protective, homeostatic and immunoregulatory properties, although our knowledge about the equivalent antibodies in humans has been much more limited. In the current study, human monoclonal a...

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Autores principales: Grönwall, Caroline, Charles, Edgar D., Dustin, Lynn B., Rader, Christoph, Silverman, Gregg J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3997490/
https://www.ncbi.nlm.nih.gov/pubmed/24760047
http://dx.doi.org/10.1371/journal.pone.0095999
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author Grönwall, Caroline
Charles, Edgar D.
Dustin, Lynn B.
Rader, Christoph
Silverman, Gregg J.
author_facet Grönwall, Caroline
Charles, Edgar D.
Dustin, Lynn B.
Rader, Christoph
Silverman, Gregg J.
author_sort Grönwall, Caroline
collection PubMed
description Autoreactive antibodies that recognize neo-determinants on apoptotic cells in mice have been proposed to have protective, homeostatic and immunoregulatory properties, although our knowledge about the equivalent antibodies in humans has been much more limited. In the current study, human monoclonal antibodies with binding specificity for apoptotic cells were isolated from the bone marrow of healthy adults using phage display technology. These antibodies were shown to recognize phosphorylcholine (PC)-associated neo-determinants. Interestingly, three of the four identified apoptotic cell-specific antibody clones were encoded by VH3 region rearrangements with germline or nearly germline configuration without evidence of somatic hypermutation. Importantly, the different identified antibody clones had diverse heavy chain CDR3 and deduced binding surfaces as suggested by structure modeling. This may suggest a potentially great heterogeneity in human antibodies recognizing PC-related epitopes on apoptotic cells. To re-construct the postulated structural format of the parental anti-PC antibody, the dominant clone was also expressed as a recombinant human polymeric IgM, which revealed a substantially increased binding reactivity, with dose-dependent and antigen-inhibitable binding of apoptotic cells. Our findings may have implication for improved prognostic testing and therapeutic interventions in human inflammatory disease.
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spelling pubmed-39974902014-04-29 Selection of Apoptotic Cell Specific Human Antibodies from Adult Bone Marrow Grönwall, Caroline Charles, Edgar D. Dustin, Lynn B. Rader, Christoph Silverman, Gregg J. PLoS One Research Article Autoreactive antibodies that recognize neo-determinants on apoptotic cells in mice have been proposed to have protective, homeostatic and immunoregulatory properties, although our knowledge about the equivalent antibodies in humans has been much more limited. In the current study, human monoclonal antibodies with binding specificity for apoptotic cells were isolated from the bone marrow of healthy adults using phage display technology. These antibodies were shown to recognize phosphorylcholine (PC)-associated neo-determinants. Interestingly, three of the four identified apoptotic cell-specific antibody clones were encoded by VH3 region rearrangements with germline or nearly germline configuration without evidence of somatic hypermutation. Importantly, the different identified antibody clones had diverse heavy chain CDR3 and deduced binding surfaces as suggested by structure modeling. This may suggest a potentially great heterogeneity in human antibodies recognizing PC-related epitopes on apoptotic cells. To re-construct the postulated structural format of the parental anti-PC antibody, the dominant clone was also expressed as a recombinant human polymeric IgM, which revealed a substantially increased binding reactivity, with dose-dependent and antigen-inhibitable binding of apoptotic cells. Our findings may have implication for improved prognostic testing and therapeutic interventions in human inflammatory disease. Public Library of Science 2014-04-23 /pmc/articles/PMC3997490/ /pubmed/24760047 http://dx.doi.org/10.1371/journal.pone.0095999 Text en © 2014 Grönwall et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Grönwall, Caroline
Charles, Edgar D.
Dustin, Lynn B.
Rader, Christoph
Silverman, Gregg J.
Selection of Apoptotic Cell Specific Human Antibodies from Adult Bone Marrow
title Selection of Apoptotic Cell Specific Human Antibodies from Adult Bone Marrow
title_full Selection of Apoptotic Cell Specific Human Antibodies from Adult Bone Marrow
title_fullStr Selection of Apoptotic Cell Specific Human Antibodies from Adult Bone Marrow
title_full_unstemmed Selection of Apoptotic Cell Specific Human Antibodies from Adult Bone Marrow
title_short Selection of Apoptotic Cell Specific Human Antibodies from Adult Bone Marrow
title_sort selection of apoptotic cell specific human antibodies from adult bone marrow
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3997490/
https://www.ncbi.nlm.nih.gov/pubmed/24760047
http://dx.doi.org/10.1371/journal.pone.0095999
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