UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

Plasma cell but not CD20-mediated B cell depletion protects from bleomycin-induced lung fibrosis

Prêle, Cecilia M; Miles, Tylah; Pearce, David R; O'Donoghue, Robert J; Grainge, Chris; Barrett, Lucy; Birnie, Kimberly; ... Mutsaers, Steven E; + view all (2022) Plasma cell but not CD20-mediated B cell depletion protects from bleomycin-induced lung fibrosis. European Respiratory Journal , 60 (5) , Article 2101469. 10.1183/13993003.01469-2021. Green open access

[thumbnail of Pearce_13993003.01469-2021.full.pdf]
Preview
Text
Pearce_13993003.01469-2021.full.pdf

Download (2MB) | Preview

Abstract

Idiopathic pulmonary fibrosis (IPF) is an interstitial lung disease associated with chronic inflammation and tissue remodelling leading to fibrosis, reduced pulmonary function, respiratory failure and death. Bleomycin (Blm)-induced lung fibrosis in mice replicates several clinical features of human IPF, including prominent lymphoid aggregates of predominantly B cells that accumulate in the lung adjacent to areas of active fibrosis. We have previously shown a requirement for B cells in the development of Blm-induced lung fibrosis in mice. To determine the therapeutic potential of inhibiting B cell function in pulmonary fibrosis, we examined the effects of anti-CD20 B-cell ablation therapy to selectively remove mature B cells from the immune system and inhibit Blm-induced lung fibrosis. Anti-CD20-B cell ablation did not reduce fibrosis in this model, however immune phenotyping of peripheral blood and lung resident cells revealed that anti-CD20 treated mice retained a high frequency of CD19+ CD138+ plasma cells (PCs). Interestingly, high levels of CD138+ cells were also identified in the lung tissue of patients with IPF, consistent with the mouse model. Treatment of mice with bortezomib, which depletes PCs, reduced the level of Blm-induced lung fibrosis, implicating PCs as important effector cells in the development and progression of pulmonary fibrosis.

Type: Article
Title: Plasma cell but not CD20-mediated B cell depletion protects from bleomycin-induced lung fibrosis
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1183/13993003.01469-2021
Publisher version: https://doi.org/10.1183/13993003.01469-2021
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
UCL classification: UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Respiratory Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Oncology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
URI: https://discovery.ucl.ac.uk/id/eprint/10153139
Downloads since deposit
5Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item