Cell Reports (Jun 2023)
Extrafollicular IgD−CD27−CXCR5−CD11c− DN3 B cells infiltrate inflamed tissues in autoimmune fibrosis and in severe COVID-19
- Hugues Allard-Chamard,
- Naoki Kaneko,
- Alice Bertocchi,
- Na Sun,
- Julie Boucau,
- Hsiao-Hsuan Kuo,
- Jocelyn R. Farmer,
- Cory Perugino,
- Vinay S. Mahajan,
- Samuel J.H. Murphy,
- Katherine Premo,
- Thomas Diefenbach,
- Musie Ghebremichael,
- Grace Yuen,
- Alekhya Kotta,
- Zafer Akman,
- Mathias Lichterfeld,
- Bruce D. Walker,
- Xu G. Yu,
- Masafumi Moriyama,
- Takashi Maehara,
- Seiji Nakamura,
- John H. Stone,
- Robert F. Padera,
- Shiv Pillai
Affiliations
- Hugues Allard-Chamard
- 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
- Naoki Kaneko
- 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
- Alice Bertocchi
- Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA
- Na Sun
- Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA
- Julie Boucau
- Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA
- Hsiao-Hsuan Kuo
- Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA
- Jocelyn R. Farmer
- Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA
- Cory Perugino
- Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA; Division of Rheumatology Allergy and Immunology, Massachusetts General Hospital, Boston, MA 02114, USA
- Vinay S. Mahajan
- Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA; Department of Pathology, Brigham and Women’s Hospital, Boston, MA 02115, USA
- Samuel J.H. Murphy
- Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA
- Katherine Premo
- Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA
- Thomas Diefenbach
- Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA
- Musie Ghebremichael
- Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA
- Grace Yuen
- Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA
- Alekhya Kotta
- Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA
- Zafer Akman
- Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA
- Mathias Lichterfeld
- Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA; Department of Medicine, Brigham and Women’s Hospital, Boston, MA 02115, USA
- Bruce D. Walker
- 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
- Xu G. Yu
- Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA
- Masafumi Moriyama
- Section of Oral and Maxillofacial Oncology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University, Fukuoka, Japan
- Takashi Maehara
- 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
- Seiji Nakamura
- Section of Oral and Maxillofacial Oncology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University, Fukuoka, Japan
- John H. Stone
- Division of Rheumatology Allergy and Immunology, Massachusetts General Hospital, Boston, MA 02114, USA
- Robert F. Padera
- Department of Pathology, Brigham and Women’s Hospital, Boston, MA 02115, USA
- Shiv Pillai
- Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA; Corresponding author
- Journal volume & issue
-
Vol. 42,
no. 6
p. 112630
Abstract
Summary: 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)−CD27−CXCR5−CD11c+ DN2 B cell subset has been previously studied in some autoimmune diseases. A distinct IgD−CD27−CXCR5−CD11c− 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.
