Extrafollicular IgD−CD27−CXCR5−CD11c− DN3 B cells infiltrate inflamed tissues in autoimmune fibrosis and in severe COVID-19,Cell Reports

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Extrafollicular IgD−CD27−CXCR5−CD11c− DN3 B cells infiltrate inflamed tissues in autoimmune fibrosis and in severe COVID-19
Cell Reports ( IF 7.5 ) Pub Date : 2023-05-30 , DOI: 10.1016/j.celrep.2023.112630
Hugues Allard-Chamard ₁ , Naoki Kaneko ₂ , Alice Bertocchi ₃ , Na Sun ₃ , Julie Boucau ₃ , Hsiao-Hsuan Kuo ₃ , Jocelyn R Farmer ₃ , Cory Perugino ₄ , Vinay S Mahajan ₅ , Samuel J H Murphy ₃ , Katherine Premo ₃ , Thomas Diefenbach ₃ , Musie Ghebremichael ₃ , Grace Yuen ₃ , Alekhya Kotta ₃ , Zafer Akman ₃ , Mathias Lichterfeld ₆ , Bruce D Walker ₇ , Xu G Yu ₃ , Masafumi Moriyama ₈ , Takashi Maehara ₂ , Seiji Nakamura ₈ , John H Stone ₉ , Robert F Padera ₁₀ , Shiv Pillai ₃

Affiliation

Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA; Division of Rheumatology, Faculté de médecine et des sciences de la santé de l'Université de Sherbrooke et Centre de Recherche Clinique Étienne-Le Bel, Sherbrooke, QC J1K 2R1, Canada.
Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA; Section of Oral and Maxillofacial Oncology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University, Fukuoka, Japan.
Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.
Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA; Division of Rheumatology Allergy and Immunology, Massachusetts General Hospital, Boston, MA 02114, USA.
Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA; Department of Pathology, Brigham and Women's Hospital, Boston, MA 02115, USA.
Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA; Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.
Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA; Department of Biology and Institute of Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Section of Oral and Maxillofacial Oncology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University, Fukuoka, Japan.
Division of Rheumatology Allergy and Immunology, Massachusetts General Hospital, Boston, MA 02114, USA.
Department of Pathology, Brigham and Women's Hospital, Boston, MA 02115, USA.

Although therapeutic B cell depletion dramatically resolves inflammation in many diseases in which antibodies appear not to play a central role, distinct extrafollicular pathogenic B cell subsets that accumulate in disease lesions have hitherto not been identified. The circulating immunoglobulin D (IgD)CD27CXCR5CD11c DN2 B cell subset has been previously studied in some autoimmune diseases. A distinct IgDCD27CXCR5CD11c DN3 B cell subset accumulates in the blood both in IgG4-related disease, an autoimmune disease in which inflammation and fibrosis can be reversed by B cell depletion, and in severe COVID-19. These DN3 B cells prominently accumulate in the end organs of IgG4-related disease and in lung lesions in COVID-19, and double-negative B cells prominently cluster with CD4 T cells in these lesions. Extrafollicular DN3 B cells may participate in tissue inflammation and fibrosis in autoimmune fibrotic diseases, as well as in COVID-19.

中文翻译：

滤泡外 IgD−CD27−CXCR5−CD11c− DN3 B 细胞在自身免疫性纤维化和严重的 COVID-19 中浸润发炎组织

尽管治疗性 B 细胞耗竭可显着解决许多疾病中的炎症，而在这些疾病中，抗体似乎不发挥核心作用，但迄今为止，尚未鉴定出在疾病病变中积累的独特滤泡外致病性 B 细胞亚群。循环免疫球蛋白 D (IgD)CD27CXCR5CD11c DN2 B 细胞亚群先前已在一些自身免疫性疾病中进行过研究。在 IgG4 相关疾病（一种可通过 B 细胞耗竭逆转炎症和纤维化的自身免疫性疾病）和严重的 COVID-19 中，血液中都会积聚独特的 IgDCD27CXCR5CD11c DN3 B 细胞亚群。这些 DN3 B 细胞主要积聚在 IgG4 相关疾病的终末器官和 COVID-19 的肺部病变中，并且双阴性 B 细胞在这些病变中与 CD4 T 细胞明显聚集。滤泡外 DN3 B 细胞可能参与自身免疫性纤维化疾病以及 COVID-19 中的组织炎症和纤维化。

更新日期：2023-05-30

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