Plasma cell and regulatory B Cell-infiltration in the lungs of Bleomycin-treated mice

Prêle, C., Pearce, D., Miles, T., O'Donoghue, R., Lucas, A., Fear, M., Ernst, M., Laurent, G., Knight, D., Hoyne, G., McAnulty, R. and Mutsaers, S. (2018) Plasma cell and regulatory B Cell-infiltration in the lungs of Bleomycin-treated mice. Respirology, 23 (Supp. 1). p. 70.

Abstract

Introduction
STAT3 and B cells are implicated in the development of lung fibrosis. We have previously demonstrated that hyper-activated STAT3, B cell-deficient gp130757F;μMT-/- mice are protected from bleomycin (BLM)-induced lung fibrosis suggesting that B cells are important in the regulation of STAT3-mediated fibrosis.

Hypothesis
We hypothesise that the pro-fibrotic effects of STAT3 involve B cell-mediated immune regulation.

Methods
The effect of anti-CD20 therapy in bleomycin-treated wildtype and gp130757F mice on lung fibrosis and immune cell composition was examined. Mice were given two 100μg doses of anti-CD20 antibody (Genentech Inc USA) or IgG2a isotype control i.p. either 7 days prior to and 7 days after bleomycin or on day 10 and day 19 post-bleomycin treatment (following the initiation of fibrosis), and the extent of fibrosis measured at 28 days.

Results
FACS analysis of blood taken on days 0, 7 and 28 days post-bleomycin-treatment revealed an almost complete depletion of CD19+ B cells in the circulation of wildtype mice but not gp130757F. However, the extent of fibrosis, assessed using micro-CT imaging and HPLC analysis of hydroxyproline levels was not significantly different between treatment groups. Histological analysis revealed an abundance of CD5+ B cells and CD138+ (plasma cells) in the lungs of the anti-CD20-treated mice. FACS analysis identified an expansion of CD138+ (days 7 and 28) and CD5+ cells in the lungs of bleomycin treated mice at day 28.

Conclusion
Although antibody depletion of follicular B cells had no effect on bleomycin-induced fibrosis, residual CD138+ plasma cells and CD5+ B are abundant in the lungs of bleomycin-treated mice. The activity of these B cell subsets may contribute to the fibrotic phenotype.

Grant Support: This work is funded by NHMRC Project Grant GNT1067511 and British Lung Foundation Grant PPRG15-10.

Item Type:	Journal Article
Publisher:	Wiley-Blackwell
Copyright:	© 2018 Asian Pacific Society of Respirology
Other Information:	Oral presentation given @ The Australia & New Zealand Society of Respiratory Science and The Thoracic Society of Australia and New Zealand (ANZSRS/TSANZ) Annual Scientific Meeting, Adelaide, Australia, 23–27 March 2018
URI:	http://researchrepository.murdoch.edu.au/id/eprint/64319

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