Human T-bet governs the generation of a distinct subset of CD11c


Journal

Science immunology
ISSN: 2470-9468
Titre abrégé: Sci Immunol
Pays: United States
ID NLM: 101688624

Informations de publication

Date de publication:
22 07 2022
Historique:
entrez: 22 7 2022
pubmed: 23 7 2022
medline: 27 7 2022
Statut: ppublish

Résumé

High-level expression of the transcription factor T-bet characterizes a phenotypically distinct murine B cell population known as "age-associated B cells" (ABCs). T-bet-deficient mice have reduced ABCs and impaired humoral immunity. We describe a patient with inherited T-bet deficiency and largely normal humoral immunity including intact somatic hypermutation, affinity maturation and memory B cell formation in vivo, and B cell differentiation into Ig-producing plasmablasts in vitro. Nevertheless, the patient exhibited skewed class switching to IgG1, IgG4, and IgE, along with reduced IgG2, both in vivo and in vitro. Moreover, T-bet was required for the in vivo and in vitro development of a distinct subset of human B cells characterized by reduced expression of CD21 and the concomitantly high expression of CD19, CD20, CD11c, FCRL5, and T-bet, a phenotype that shares many features with murine ABCs. Mechanistically, human T-bet governed CD21

Identifiants

pubmed: 35867801
doi: 10.1126/sciimmunol.abq3277
pmc: PMC9413977
mid: NIHMS1828447
doi:

Substances chimiques

Adaptor Proteins, Signal Transducing 0
CD11c Antigen 0
Dapp1 protein, mouse 0
Immunoglobulin G 0
Lipoproteins 0

Types de publication

Case Reports Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

eabq3277

Subventions

Organisme : Howard Hughes Medical Institute
Pays : United States
Organisme : NIAID NIH HHS
ID : R37 AI095983
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001866
Pays : United States

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Auteurs

Rui Yang (R)

St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, Rockefeller University, New York, NY 10065, USA.
Department of Pediatrics, Weill Cornell Medicine, New York, NY 10065, USA.

Danielle T Avery (DT)

Garvan Institute of Medical Research, Darlinghurst, NSW 2010 Australia.

Katherine J L Jackson (KJL)

Garvan Institute of Medical Research, Darlinghurst, NSW 2010 Australia.

Masato Ogishi (M)

St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, Rockefeller University, New York, NY 10065, USA.

Ibtihal Benhsaien (I)

Laboratory of Clinical Immunology, Inflammation, and Allergy, Faculty of Medicine and Pharmacy of Casablanca, King Hassan II University, 20460 Casablanca, Morocco.
Clinical Immunology Unit, Department of Pediatric Infectious Diseases, Children's Hospital, CHU Averroes, 20460 Casablanca, Morocco.

Likun Du (L)

Department of Biosciences and Nutrition, Karolinska Institutet, 14183 Huddinge, Sweden.

Xiaofei Ye (X)

Department of Biosciences and Nutrition, Karolinska Institutet, 14183 Huddinge, Sweden.

Jing Han (J)

St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, Rockefeller University, New York, NY 10065, USA.

Jérémie Rosain (J)

Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM UMR 1163, Necker Hospital for Sick Children, 75015 Paris, France.
Paris Cité University, Imagine Institute, 75015 Paris, France.

Jessica N Peel (JN)

St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, Rockefeller University, New York, NY 10065, USA.

Marie-Alexandra Alyanakian (MA)

Immunology Laboratory, Necker Hospital for Sick Children, Assistance Publique-Hôpitaux de Paris (AP-HP), 75015 Paris, France.

Bénédicte Neven (B)

Department of Pediatric Immunology, Hematology, and Rheumatology, Necker Hospital for Sick Children, AP-HP, Paris, France.

Sarah Winter (S)

Paris Cité University, Imagine Institute, 75015 Paris, France.
Laboratory of Lymphocyte Activation and Susceptibility to EBV Infection, INSERM UMR 1163, Imagine Institute, 75015 Paris, France.

Anne Puel (A)

St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, Rockefeller University, New York, NY 10065, USA.
Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM UMR 1163, Necker Hospital for Sick Children, 75015 Paris, France.
Paris Cité University, Imagine Institute, 75015 Paris, France.

Bertrand Boisson (B)

St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, Rockefeller University, New York, NY 10065, USA.
Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM UMR 1163, Necker Hospital for Sick Children, 75015 Paris, France.
Paris Cité University, Imagine Institute, 75015 Paris, France.

Kathryn J Payne (KJ)

Garvan Institute of Medical Research, Darlinghurst, NSW 2010 Australia.

Melanie Wong (M)

Children's Hospital at Westmead, Westmead, NSW, Australia.
Faculty of Medicine, University of Sydney, Sydney, NSW, Australia.

Amanda J Russell (AJ)

Garvan Institute of Medical Research, Darlinghurst, NSW 2010 Australia.

Yoko Mizoguchi (Y)

Department of Pediatrics, Hiroshima University, Graduate School of Biomedical and Health Sciences, Hiroshima, Japan.

Satoshi Okada (S)

Department of Pediatrics, Hiroshima University, Graduate School of Biomedical and Health Sciences, Hiroshima, Japan.

Gulbu Uzel (G)

Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.

Christopher C Goodnow (CC)

Garvan Institute of Medical Research, Darlinghurst, NSW 2010 Australia.
St. Vincent's Clinical School, Faculty of Medicine, UNSW Sydney, Darlinghurst, NSW 2010, Australia.

Sylvain Latour (S)

Paris Cité University, Imagine Institute, 75015 Paris, France.
Laboratory of Lymphocyte Activation and Susceptibility to EBV Infection, INSERM UMR 1163, Imagine Institute, 75015 Paris, France.

Jalila El Bakkouri (J)

Laboratory of Clinical Immunology, Inflammation, and Allergy, Faculty of Medicine and Pharmacy of Casablanca, King Hassan II University, 20460 Casablanca, Morocco.
Clinical Immunology Unit, Department of Pediatric Infectious Diseases, Children's Hospital, CHU Averroes, 20460 Casablanca, Morocco.

Aziz Bousfiha (A)

Laboratory of Clinical Immunology, Inflammation, and Allergy, Faculty of Medicine and Pharmacy of Casablanca, King Hassan II University, 20460 Casablanca, Morocco.
Clinical Immunology Unit, Department of Pediatric Infectious Diseases, Children's Hospital, CHU Averroes, 20460 Casablanca, Morocco.

Kahn Preece (K)

John Hunter Children's Hospital, Newcastle, NSW, Australia.

Paul E Gray (PE)

School of Women's and Children's Health, UNSW Sydney, Sydney, NSW, Australia.
Department of Immunology and Infectious Diseases, Sydney Children's Hospital, Sydney, NSW, Australia.

Baerbel Keller (B)

Department of Rheumatology and Clinical Immunology, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Center for Chronic Immunodeficiency (CCI), Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.

Klaus Warnatz (K)

Department of Rheumatology and Clinical Immunology, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Center for Chronic Immunodeficiency (CCI), Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.

Stéphanie Boisson-Dupuis (S)

St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, Rockefeller University, New York, NY 10065, USA.
Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM UMR 1163, Necker Hospital for Sick Children, 75015 Paris, France.
Paris Cité University, Imagine Institute, 75015 Paris, France.

Laurent Abel (L)

St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, Rockefeller University, New York, NY 10065, USA.
Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM UMR 1163, Necker Hospital for Sick Children, 75015 Paris, France.
Paris Cité University, Imagine Institute, 75015 Paris, France.

Qiang Pan-Hammarström (Q)

Department of Biosciences and Nutrition, Karolinska Institutet, 14183 Huddinge, Sweden.

Jacinta Bustamante (J)

St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, Rockefeller University, New York, NY 10065, USA.
Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM UMR 1163, Necker Hospital for Sick Children, 75015 Paris, France.
Paris Cité University, Imagine Institute, 75015 Paris, France.
Study Center for Primary Immunodeficiencies, Necker Hospital for Sick Children, AP-HP, 75015 Paris, France.

Cindy S Ma (CS)

Garvan Institute of Medical Research, Darlinghurst, NSW 2010 Australia.
St. Vincent's Clinical School, Faculty of Medicine, UNSW Sydney, Darlinghurst, NSW 2010, Australia.

Jean-Laurent Casanova (JL)

St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, Rockefeller University, New York, NY 10065, USA.
Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM UMR 1163, Necker Hospital for Sick Children, 75015 Paris, France.
Paris Cité University, Imagine Institute, 75015 Paris, France.
Howard Hughes Medical Institute, New York, NY 10065, USA.
Department of Pediatrics, Necker Hospital for Sick Children, AP-HP, 75015 Paris, France.

Stuart G Tangye (SG)

Garvan Institute of Medical Research, Darlinghurst, NSW 2010 Australia.
St. Vincent's Clinical School, Faculty of Medicine, UNSW Sydney, Darlinghurst, NSW 2010, Australia.

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