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

doi:10.1016/j.celrep.2023.112630

Extrafollicular IgD^-CD27^-CXCR5^-CD11c^- DN3 B cells infiltrate inflamed tissues in autoimmune fibrosis and in severe COVID-19

Cell Rep. 2023 Jun 27;42(6):112630. doi: 10.1016/j.celrep.2023.112630. Epub 2023 May 30.

Authors

Hugues Allard-Chamard¹, Naoki Kaneko², Alice Bertocchi³, Na Sun³, Julie Boucau³, Hsiao-Hsuan Kuo³, Jocelyn R Farmer³, Cory Perugino⁴, Vinay S Mahajan⁵, Samuel J H Murphy³, Katherine Premo³, Thomas Diefenbach³, Musie Ghebremichael³, Grace Yuen³, Alekhya Kotta³, Zafer Akman³, Mathias Lichterfeld⁶, Bruce D Walker⁷, Xu G Yu³, Masafumi Moriyama⁸, Takashi Maehara², Seiji Nakamura⁸, John H Stone⁹, Robert F Padera¹⁰, Shiv Pillai¹¹

Affiliations

¹ 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.
² 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.
³ Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.
⁴ Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA; Division of Rheumatology Allergy and Immunology, Massachusetts General Hospital, Boston, MA 02114, USA.
⁵ Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA; Department of Pathology, Brigham and Women's Hospital, Boston, MA 02115, USA.
⁶ Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA; Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.
⁷ 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.
⁸ Section of Oral and Maxillofacial Oncology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University, Fukuoka, Japan.
⁹ Division of Rheumatology Allergy and Immunology, Massachusetts General Hospital, Boston, MA 02114, USA.
¹⁰ Department of Pathology, Brigham and Women's Hospital, Boston, MA 02115, USA.
¹¹ Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA. Electronic address: pillai@helix.mgh.harvard.edu.

Abstract

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.

Keywords: B cell depletion in disease; COVID-19 pathogenesis; CP: Immunology; DN3 B cells; IgG4-related disease; T-B collaboration in disease; double-negative B cells; extrafollicular B cells; inflammatory fibrosis.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

B-Lymphocyte Subsets* / metabolism
B-Lymphocyte Subsets* / pathology
COVID-19*
Fibrosis
Humans
Immunoglobulin D
Immunoglobulin G4-Related Disease*
Inflammation
Receptors, CXCR5

Substances

CXCR5 protein, human
Immunoglobulin D
Receptors, CXCR5

Abstract

Publication types

MeSH terms

Substances

Grants and funding