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

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.

Spatially resolved multiomics of human cardiac niches

“…16E ). This suggests that plasma B cells in the epicardium may contribute to ECM formation, consistent with a previous study showing the role of plasma B cells in fibrosis 82 .…”

WITHDRAWN: Causal relationship between immune cells and idiopathic pulmonary fibrosis based on Mendelian randomization analysis

“…Anti-CD20 antibody rituximab treatment of B-cell tumors and related autoimmune diseases [21]. Inhibition of CD20 B cells in bleomycin-induced pulmonary brosis by removal of mature B cells by ablative therapy [22]. CD28 on activated Tregs is a CD28 subpopulation distributed on the surface of regulatory T cells, whose expansion is dependent on the T-cell receptor (TCR) and the CD28 signaling pathway, generating antigen speci city and effectively inhibiting the proliferation of effector T cells.…”

The emerging roles and therapeutic potential of B cells in sepsis

“…B-cell depletion therapy has been shown to suppress excessive inflammation in inflammatory diseases, but this approach eliminates nearly all B cells in the body and is not suitable for sepsis ( Lee et al, 2021 ). However, recent studies have shown that treatment of mice with plasma cell-depleted bortezomib, but not with anti-CD20-B cells ablation, prevents bleomycin-induced pulmonary fibrosis ( Prêle et al, 2022 ). Similarly, lethally irradiated mice lacking MZ B cells were resistant to LPS-induced endotoxic shock ( Honda et al, 2016 ).…”