Cargando…
Microarray-guided evaluation of the frequency, B-cell origins, and selectivity of human glycan-binding antibodies reveals new insights and novel antibodies
The immune system produces a diverse collection of antiglycan antibodies that are critical for host defense. At present, however, we know very little about the binding properties, origins, and sequences of these antibodies because of a lack of access to a variety of defined individual antibodies. To...
Autores principales: | , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society for Biochemistry and Molecular Biology
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9576894/ https://www.ncbi.nlm.nih.gov/pubmed/36087840 http://dx.doi.org/10.1016/j.jbc.2022.102468 |
_version_ | 1784811631092432896 |
---|---|
author | Temme, J. Sebastian Crainic, Jennifer A. Walker, Laura M. Yang, Weizhun Tan, Zibin Huang, Xuefei Gildersleeve, Jeffrey C. |
author_facet | Temme, J. Sebastian Crainic, Jennifer A. Walker, Laura M. Yang, Weizhun Tan, Zibin Huang, Xuefei Gildersleeve, Jeffrey C. |
author_sort | Temme, J. Sebastian |
collection | PubMed |
description | The immune system produces a diverse collection of antiglycan antibodies that are critical for host defense. At present, however, we know very little about the binding properties, origins, and sequences of these antibodies because of a lack of access to a variety of defined individual antibodies. To address this challenge, we used a glycan microarray with over 800 different components to screen a panel of 516 human monoclonal antibodies that had been randomly cloned from different B-cell subsets originating from healthy human subjects. We obtained 26 antiglycan antibodies, most of which bound microbial carbohydrates. The majority of the antiglycan antibodies identified in the screen displayed selective binding for specific glycan motifs on our array and lacked polyreactivity. We found that antiglycan antibodies were about twice as likely than expected to originate from IgG(+) memory B cells, whereas none were isolated from naïve, early emigrant, or immature B cells. Therefore, our results indicate that certain B-cell subsets in our panel are enriched in antiglycan antibodies, and IgG(+) memory B cells may be a promising source of such antibodies. Furthermore, some of the newly identified antibodies bound glycans for which there are no reported monoclonal antibodies available, and these may be useful as research tools, diagnostics, or therapeutic agents. Overall, the results provide insight into the types and properties of antiglycan antibodies produced by the human immune system and a framework for the identification of novel antiglycan antibodies in the future. |
format | Online Article Text |
id | pubmed-9576894 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | American Society for Biochemistry and Molecular Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-95768942022-10-19 Microarray-guided evaluation of the frequency, B-cell origins, and selectivity of human glycan-binding antibodies reveals new insights and novel antibodies Temme, J. Sebastian Crainic, Jennifer A. Walker, Laura M. Yang, Weizhun Tan, Zibin Huang, Xuefei Gildersleeve, Jeffrey C. J Biol Chem Research Article The immune system produces a diverse collection of antiglycan antibodies that are critical for host defense. At present, however, we know very little about the binding properties, origins, and sequences of these antibodies because of a lack of access to a variety of defined individual antibodies. To address this challenge, we used a glycan microarray with over 800 different components to screen a panel of 516 human monoclonal antibodies that had been randomly cloned from different B-cell subsets originating from healthy human subjects. We obtained 26 antiglycan antibodies, most of which bound microbial carbohydrates. The majority of the antiglycan antibodies identified in the screen displayed selective binding for specific glycan motifs on our array and lacked polyreactivity. We found that antiglycan antibodies were about twice as likely than expected to originate from IgG(+) memory B cells, whereas none were isolated from naïve, early emigrant, or immature B cells. Therefore, our results indicate that certain B-cell subsets in our panel are enriched in antiglycan antibodies, and IgG(+) memory B cells may be a promising source of such antibodies. Furthermore, some of the newly identified antibodies bound glycans for which there are no reported monoclonal antibodies available, and these may be useful as research tools, diagnostics, or therapeutic agents. Overall, the results provide insight into the types and properties of antiglycan antibodies produced by the human immune system and a framework for the identification of novel antiglycan antibodies in the future. American Society for Biochemistry and Molecular Biology 2022-09-08 /pmc/articles/PMC9576894/ /pubmed/36087840 http://dx.doi.org/10.1016/j.jbc.2022.102468 Text en https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Research Article Temme, J. Sebastian Crainic, Jennifer A. Walker, Laura M. Yang, Weizhun Tan, Zibin Huang, Xuefei Gildersleeve, Jeffrey C. Microarray-guided evaluation of the frequency, B-cell origins, and selectivity of human glycan-binding antibodies reveals new insights and novel antibodies |
title | Microarray-guided evaluation of the frequency, B-cell origins, and selectivity of human glycan-binding antibodies reveals new insights and novel antibodies |
title_full | Microarray-guided evaluation of the frequency, B-cell origins, and selectivity of human glycan-binding antibodies reveals new insights and novel antibodies |
title_fullStr | Microarray-guided evaluation of the frequency, B-cell origins, and selectivity of human glycan-binding antibodies reveals new insights and novel antibodies |
title_full_unstemmed | Microarray-guided evaluation of the frequency, B-cell origins, and selectivity of human glycan-binding antibodies reveals new insights and novel antibodies |
title_short | Microarray-guided evaluation of the frequency, B-cell origins, and selectivity of human glycan-binding antibodies reveals new insights and novel antibodies |
title_sort | microarray-guided evaluation of the frequency, b-cell origins, and selectivity of human glycan-binding antibodies reveals new insights and novel antibodies |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9576894/ https://www.ncbi.nlm.nih.gov/pubmed/36087840 http://dx.doi.org/10.1016/j.jbc.2022.102468 |
work_keys_str_mv | AT temmejsebastian microarrayguidedevaluationofthefrequencybcelloriginsandselectivityofhumanglycanbindingantibodiesrevealsnewinsightsandnovelantibodies AT crainicjennifera microarrayguidedevaluationofthefrequencybcelloriginsandselectivityofhumanglycanbindingantibodiesrevealsnewinsightsandnovelantibodies AT walkerlauram microarrayguidedevaluationofthefrequencybcelloriginsandselectivityofhumanglycanbindingantibodiesrevealsnewinsightsandnovelantibodies AT yangweizhun microarrayguidedevaluationofthefrequencybcelloriginsandselectivityofhumanglycanbindingantibodiesrevealsnewinsightsandnovelantibodies AT tanzibin microarrayguidedevaluationofthefrequencybcelloriginsandselectivityofhumanglycanbindingantibodiesrevealsnewinsightsandnovelantibodies AT huangxuefei microarrayguidedevaluationofthefrequencybcelloriginsandselectivityofhumanglycanbindingantibodiesrevealsnewinsightsandnovelantibodies AT gildersleevejeffreyc microarrayguidedevaluationofthefrequencybcelloriginsandselectivityofhumanglycanbindingantibodiesrevealsnewinsightsandnovelantibodies |