| Author | Minghui, He | |
| Author | Saeed, Mezida B. | |
| Author | Record, Julien | |
| Author | Keszei, Marton | |
| Author | Pinho, Lia Gonc¸alves | |
| Author | Fontes, Larissa Vasconcelos | |
| Author | D`Aurelio, Roberta | |
| Author | Vieira, Raissa | |
| Author | Oliveira, Mariana M. S. | |
| Author | Geyer, Chiara | |
| Author | Bohaumilitzky, Lena | |
| Author | Thiemann, Meike | |
| Author | Deordieva, Ekaterina | |
| Author | Buedts, Lieselot | |
| Author | Lopes, Joao Pedro Matias | |
| Author | Pershin, Dmitry | |
| Author | Hammarström, Lennart | |
| Author | Xia, Yu | |
| Author | Zhao, Xiaodong | |
| Author | Cunningham-Rundles, Charlotte | |
| Author | Thrasher, Adrian J. | |
| Author | Burns, Siobhan O. | |
| Author | Almeida, Vinicius Cotta de | |
| Author | Liu, Chaohong | |
| Author | Shcherbina, Anna | |
| Author | Vandenberghe, Peter | |
| Author | Westerberg, Lisa S. | |
| Access date | 2022-10-03T15:04:04Z | |
| Available date | 2022-10-03T15:04:04Z | |
| Document date | 2022 | |
| Citation | Minghui, He et al. Overactive WASp in X-linked neutropenia leads to aberrant B-cell division and accelerated plasma cell generation. J. Allergy Clin. Immunol., v. 149, n. 3, p. 1 - 16, Mar. 2022. | en_US |
| ISSN | 0091-6749 | en_US |
| URI | https://www.arca.fiocruz.br/handle/icict/54969 | |
| Language | eng | en_US |
| Publisher | Elsevier | en_US |
| Rights | open access | |
| Subject in Portuguese | Células B | en_US |
| Subject in Portuguese | Neutropenia ligada ao X | en_US |
| Subject in Portuguese | Actina | en_US |
| Subject in Portuguese | Vespa | en_US |
| Subject in Portuguese | IgA | en_US |
| Subject in Portuguese | Centro germinativo | en_US |
| Subject in Portuguese | Células plasmáticas | en_US |
| Subject in Portuguese | Imunodeficiência primária | en_US |
| Title | Overactive WASp in X-linked neutropenia leads to aberrant B-cell division and accelerated plasma cell generation | en_US |
| Type | Article | |
| DOI | 10.1016/j.jaci.2021.07.033 | |
| Abstract | Background: B-cell affinity maturation in germinal center relies
on regulated actin dynamics for cell migration and cell-to-cell
communication. Activating mutations in the cytoskeletal
regulator Wiskott-Aldrich syndrome protein (WASp) cause
X-linked neutropenia (XLN) with reduced serum level of IgA.
Objective: We investigated the role of B cells in XLN
pathogenesis.
Methods: We examined B cells from 6 XLN patients, 2 of whom
had novel R268W and S271F mutations in WASp. By using
immunized XLN mouse models that carry the corresponding
patient mutations, WASp L272P or WASp I296T, we examined
the B-cell response.
Results: XLN patients had normal naive B cells and
plasmablasts, but reduced IgA1 B cells and memory B cells, and
poor B-cell proliferation. On immunization, XLN mice had a
2-fold reduction in germinal center B cells in spleen, but with
increased generation of plasmablasts and plasma cells. In vitro,
XLN B cells showed reduced immunoglobulin class switching
and aberrant cell division as well as increased production of
immunoglobulin-switched plasma cells.
Conclusions: Overactive WASp predisposes B cells for
premature differentiation into plasma cells at the expense of cell
proliferation and immunoglobulin class switching. ( | en_US |
| Affilliation | Department of Microbiology Tumor and Cell Biology, Karolinska Institutet, Stockholm. | en_US |
| Affilliation | Department of Microbiology Tumor and Cell Biology, Karolinska Institutet, Stockholm. | en_US |
| Affilliation | Department of Microbiology Tumor and Cell Biology, Karolinska Institutet, Stockholm. | en_US |
| Affilliation | Department of Microbiology Tumor and Cell Biology, Karolinska Institutet, Stockholm. | en_US |
| Affilliation | Department of Microbiology Tumor and Cell Biology, Karolinska Institutet, Stockholm / Fundação Oswaldo Cruz. Laboratório de Pesquisa sobre o Timo. Rio de Janeiro, RJ, Brasil. | en_US |
| Affilliation | Department of Microbiology Tumor and Cell Biology, Karolinska Institutet, Stockholm / Fundação Oswaldo Cruz. Laboratório de Pesquisa sobre o Timo. Rio de Janeiro, RJ, Brasil. | en_US |
| Affilliation | Department of Microbiology Tumor and Cell Biology, Karolinska Institutet, Stockholm. | en_US |
| Affilliation | Department of Microbiology Tumor and Cell Biology, Karolinska Institutet, Stockholm. | en_US |
| Affilliation | Department of Microbiology Tumor and Cell Biology, Karolinska Institutet, Stockholm. | en_US |
| Affilliation | Department of Microbiology Tumor and Cell Biology, Karolinska Institutet, Stockholm. | en_US |
| Affilliation | Department of Microbiology Tumor and Cell Biology, Karolinska Institutet, Stockholm. | en_US |
| Affilliation | Department of Microbiology Tumor and Cell Biology, Karolinska Institutet, Stockholm. | en_US |
| Affilliation | The Department of Immunology, Dmitry Rogachev National Medical and Research Center of Pediatric Hematology, Oncology and Immunology, Moscow | en_US |
| Affilliation | Center for Human Genetics, University Hospital Leuven, Leuven | en_US |
| Affilliation | Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York / Division of Allergy, Immunology and Rheumatology, Department of Pediatrics, UH Rainbow Babies and Children’s Hospital, Cleveland. | en_US |
| Affilliation | Department of Immunology, Dmitry Rogachev National Medical and Research Center of Pediatric Hematology, Oncology and Immunology, Moscow. | en_US |
| Affilliation | Department of Laboratory Medicine, Karolinska Institutet, Stockholm. | en_US |
| Affilliation | Department of Rheumatology and Immunology, Shenzhen Children’s Hospital, Shenzhen. | en_US |
| Affilliation | Chongqing Key Laboratory of Child Infection and Immunity, Children’s Hospital of Chongqing Medical University, Chongqing. | en_US |
| Affilliation | Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, USA. | en_US |
| Affilliation | UCL Great Ormond Street Institute of Child Health, London / Great Ormond Street Hospital for Children NHS Foundation Trust, London. | en_US |
| Affilliation | Chongqing Key Laboratory of Child Infection and Immunity, Children’s Hospital of Chongqing Medical University, Chongqing / Institute of Immunity and Transplantation, University College London, London. | en_US |
| Affilliation | Fundação Oswaldo Cruz. Laboratório de Pesquisa sobre o Timo. Rio de Janeiro, RJ, Brasil. | en_US |
| Affilliation | Department of Pathogen Biology, School of Basic Medicine, Huazhong University of Science and Technology, Wuhan. | en_US |
| Affilliation | Department of Immunology, Dmitry Rogachev National Medical and Research Center of Pediatric Hematology, Oncology and Immunology, Moscow. | en_US |
| Affilliation | Center for Human Genetics, University Hospital Leuven, Leuven. | en_US |
| Affilliation | Chongqing Key Laboratory of Child Infection and Immunity, Children’s Hospital of Chongqing Medical University, Chongqing. | en_US |
| Subject | B cells | en_US |
| Subject | X-linked neutropenia | en_US |
| Subject | Actin | en_US |
| Subject | WASp | en_US |
| Subject | IgA | en_US |
| Subject | Germinal center | en_US |
| Subject | Plasma cells | en_US |
| Subject | Primary immunodeficiency | en_US |
