Lineage Reconstruction of In Vitro Identified Antigen-Specific Autoreactive B Cells from Adaptive Immune Receptor Repertoires
The emergence, survival, growth and maintenance of autoreactive (AR) B-cell clones, the hallmark of humoral autoimmunity, leave their footprints in B-cell receptor repertoires. Collecting IgH sequences related to polyreactive (PR) ones from adaptive immune receptor repertoire (AIRR) datasets make th...
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| Published in | International journal of molecular sciences Vol. 24; no. 1; p. 225 |
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| Main Authors | , , , , |
| Format | Journal Article |
| Language | English |
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23.12.2022
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| Abstract | The emergence, survival, growth and maintenance of autoreactive (AR) B-cell clones, the hallmark of humoral autoimmunity, leave their footprints in B-cell receptor repertoires. Collecting IgH sequences related to polyreactive (PR) ones from adaptive immune receptor repertoire (AIRR) datasets make the reconstruction and analysis of PR/AR B-cell lineages possible. We developed a computational approach, named ImmChainTracer, to extract members and to visualize clonal relationships of such B-cell lineages. Our approach was successfully applied on the IgH repertoires of patients suffering from monogenic hypomorphic RAG1 and 2 deficiency (pRD) or polygenic systemic lupus erythematosus (SLE) autoimmune diseases to identify relatives of AR IgH sequences and to track their fate in AIRRs. Signs of clonal expansion, affinity maturation and class-switching events in PR/AR and non-PR/AR B-cell lineages were revealed. An extension of our method towards B-cell expansion caused by any trigger (e.g., infection, vaccination or antibody development) may provide deeper insight into antigen specific B-lymphogenesis. |
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| AbstractList | The emergence, survival, growth and maintenance of autoreactive (AR) B-cell clones, the hallmark of humoral autoimmunity, leave their footprints in B-cell receptor repertoires. Collecting IgH sequences related to polyreactive (PR) ones from adaptive immune receptor repertoire (AIRR) datasets make the reconstruction and analysis of PR/AR B-cell lineages possible. We developed a computational approach, named ImmChainTracer, to extract members and to visualize clonal relationships of such B-cell lineages. Our approach was successfully applied on the IgH repertoires of patients suffering from monogenic hypomorphic RAG1 and 2 deficiency (pRD) or polygenic systemic lupus erythematosus (SLE) autoimmune diseases to identify relatives of AR IgH sequences and to track their fate in AIRRs. Signs of clonal expansion, affinity maturation and class-switching events in PR/AR and non-PR/AR B-cell lineages were revealed. An extension of our method towards B-cell expansion caused by any trigger (e.g., infection, vaccination or antibody development) may provide deeper insight into antigen specific B-lymphogenesis. |
| Author | Walter, Jolan E Tipton, Christopher M Blazso, Peter Ujhazi, Boglarka Csomos, Krisztian |
| AuthorAffiliation | 2 Division of Pediatric Allergy/Immunology, University of South Florida at Johns Hopkins All Children’s Hospital, St. Petersburg, FL 33701, USA 1 Department of Pediatrics, University of Szeged, 6720 Szeged, Hungary 3 Department of Medicine, Division of Rheumatology, Emory University, Atlanta, GA 30322, USA 4 Division of Allergy and Immunology, Massachusetts General Hospital for Children, Boston, MA 02114, USA |
| AuthorAffiliation_xml | – name: 2 Division of Pediatric Allergy/Immunology, University of South Florida at Johns Hopkins All Children’s Hospital, St. Petersburg, FL 33701, USA – name: 3 Department of Medicine, Division of Rheumatology, Emory University, Atlanta, GA 30322, USA – name: 4 Division of Allergy and Immunology, Massachusetts General Hospital for Children, Boston, MA 02114, USA – name: 1 Department of Pediatrics, University of Szeged, 6720 Szeged, Hungary |
| Author_xml | – sequence: 1 givenname: Peter surname: Blazso fullname: Blazso, Peter organization: Division of Pediatric Allergy/Immunology, University of South Florida at Johns Hopkins All Children's Hospital, St. Petersburg, FL 33701, USA – sequence: 2 givenname: Krisztian surname: Csomos fullname: Csomos, Krisztian organization: Division of Pediatric Allergy/Immunology, University of South Florida at Johns Hopkins All Children's Hospital, St. Petersburg, FL 33701, USA – sequence: 3 givenname: Christopher M surname: Tipton fullname: Tipton, Christopher M organization: Department of Medicine, Division of Rheumatology, Emory University, Atlanta, GA 30322, USA – sequence: 4 givenname: Boglarka surname: Ujhazi fullname: Ujhazi, Boglarka organization: Division of Pediatric Allergy/Immunology, University of South Florida at Johns Hopkins All Children's Hospital, St. Petersburg, FL 33701, USA – sequence: 5 givenname: Jolan E surname: Walter fullname: Walter, Jolan E organization: Division of Allergy and Immunology, Massachusetts General Hospital for Children, Boston, MA 02114, USA |
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| Keywords | IgH repertoire autoimmunity AIRR RAG deficiency autoreactive B cells B cell lineage monoclonal antibody SLE |
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| SubjectTerms | AIRR Antibodies Autoimmune Diseases Autoimmunity autoreactive B cells B cell lineage B-Lymphocytes Humans IgH repertoire Lupus Erythematosus, Systemic monoclonal antibody |
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| Title | Lineage Reconstruction of In Vitro Identified Antigen-Specific Autoreactive B Cells from Adaptive Immune Receptor Repertoires |
| URI | https://www.ncbi.nlm.nih.gov/pubmed/36613668 https://search.proquest.com/docview/2761981792 https://pubmed.ncbi.nlm.nih.gov/PMC9820449 https://doaj.org/article/f71e73f5b0c64fc08d8b8c39d82771e2 |
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