Lineage Reconstruction of In Vitro Identified Antigen-Specific Autoreactive B Cells from Adaptive Immune Receptor Repertoires.

Humans B-Lymphocytes Autoimmunity Autoimmune Diseases Lupus Erythematosus, Systemic Antibodies
AIRR B cell lineage IgH repertoire RAG deficiency SLE autoimmunity autoreactive B cells monoclonal antibody

Journal

International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791

Informations de publication

Date de publication:
23 Dec 2022
Historique:
received: 16 11 2022
revised: 15 12 2022
accepted: 20 12 2022
entrez: 8 1 2023
pubmed: 9 1 2023
medline: 11 1 2023
Statut: epublish

Résumé

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.

Identifiants

DOI: 10.3390/ijms24010225 PMID: 36613668 PMC: PMC9820449
pubmed: 36613668
pii: ijms24010225
doi: 10.3390/ijms24010225
pmc: PMC9820449
pii:
doi:

Substances chimiques

Antibodies 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Subventions

Organisme : NIAID NIH HHS
ID : R01 AI153830
Pays : United States
Organisme : NIH HHS
ID : 5K08AI103035
Pays : United States
Organisme : NIH HHS
ID : R01AI153830-05
Pays : United States

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Auteurs

Peter Blazso (P)

Department of Pediatrics, University of Szeged, 6720 Szeged, Hungary.
Division of Pediatric Allergy/Immunology, University of South Florida at Johns Hopkins All Children's Hospital, St. Petersburg, FL 33701, USA.

Krisztian Csomos (K)

Division of Pediatric Allergy/Immunology, University of South Florida at Johns Hopkins All Children's Hospital, St. Petersburg, FL 33701, USA.

Christopher M Tipton (CM)

Department of Medicine, Division of Rheumatology, Emory University, Atlanta, GA 30322, USA.

Boglarka Ujhazi (B)

Division of Pediatric Allergy/Immunology, University of South Florida at Johns Hopkins All Children's Hospital, St. Petersburg, FL 33701, USA.

Jolan E Walter (JE)

Division of Pediatric Allergy/Immunology, University of South Florida at Johns Hopkins All Children's Hospital, St. Petersburg, FL 33701, USA.
Division of Allergy and Immunology, Massachusetts General Hospital for Children, Boston, MA 02114, USA.

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Lineage Reconstruction of In Vitro Identified...
questionsmedicales.fr › Systèmes sanguin et immunitaire › Système immunitaire › Leucocytes › Agranulocytes › Lymphocytes › Lymphocytes B › Lineage Reconstruction of In Vitro Identified...
questionsmedicales.fr › Phénomènes du système immunitaire › Immunité › Auto-immunité › Lineage Reconstruction of In Vitro Identified...
questionsmedicales.fr › Maladies du système immunitaire › Maladies auto-immunes › Lineage Reconstruction of In Vitro Identified...
questionsmedicales.fr › Maladies du système immunitaire › Maladies auto-immunes › Lupus érythémateux disséminé › Lineage Reconstruction of In Vitro Identified...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Globulines › Sérum-globulines › Immunoglobulines › Anticorps › Lineage Reconstruction of In Vitro Identified...