title: Renal recruitment of B lymphocytes exacerbates tubulointerstitial fibrosis by promoting monocyte mobilization and infiltration after unilateral ureteral obstruction.
abstract: Renal fibrosis is a significant threat to public health globally. Diverse primary aetiologies eventually result in chronic kidney disease (CKD) and immune cells influence this process. The roles of monocytes/macrophages, T cells, and mast cells have been carefully examined, whilst only a few studies have focused on the effect of B cells. We investigated B-cell function in tubulointerstitial fibrosis induced by unilateral ureteral obstruction (UUO), using genetic B-cell-deficient μMT mice or CD20 antibody-mediated B-cell-depleted mice. Obstructed kidneys of μMT and anti-CD20-treated mice showed lower levels of monocyte/macrophage infiltration and collagen deposition compared to wild-type mice. Mechanistically, anti-CD20 attenuated UUO-induced alterations of renal tumour necrosis factor-α (TNF-α), vascular cell adhesion molecule 1 (VCAM-1) pro-inflammatory genes, and CC chemokine ligand-2 (CCL2) essential for monocyte recruitment; B cells were one of the main sources of CCL2 in post-UUO kidneys. Neutralization of CCL2 reduced monocyte/macrophage influx and fibrotic changes in obstructed kidneys. Therefore, early-stage accumulation of B cells in the kidney accelerated monocyte/macrophage mobilization and infiltration, aggravating the fibrosis resulting from acutely induced kidney nephropathy. © 2016 The Authors. Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.
authors.affiliation: Department of Cardiology, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China.|Institute of Cardiovascular Diseases, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China.
authors.forename: Hui
authors.initials: H
authors.lastname: Han
authors.affiliation: Department of Cardiology, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China.
authors.forename: Jinzhou
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Department of Nephrology, Zhongshan Hospital, Shanghai Medical College, Fudan University, Shanghai, PR China.
authors.forename: Yaqiong
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Cardiology, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China.
authors.forename: Zhengbin
authors.initials: Z
authors.lastname: Zhu
authors.affiliation: Department of Cardiology, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China.|Institute of Cardiovascular Diseases, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China.
authors.forename: Yanjia
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Cardiology, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China.|Institute of Cardiovascular Diseases, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China.
authors.forename: Lin
authors.initials: L
authors.lastname: Lu
authors.affiliation: Department of Cardiology, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Jin
authors.affiliation: Department of Cardiology, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China.|Institute of Cardiovascular Diseases, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China.
authors.forename: Xiaoxiang
authors.initials: X
authors.lastname: Yan
authors.affiliation: Department of Cardiology, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China.|Institute of Cardiovascular Diseases, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China.
authors.forename: Ruiyan
authors.initials: R
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D002465:Cell Movement / Q000276:immunology; D018932:Chemokine CCL2 / Q000037:antagonists & inhibitors / Q000276:immunology; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D005355:Fibrosis; D018836:Inflammation Mediators / Q000378:metabolism; D007674:Kidney Diseases / Q000209:etiology / Q000276:immunology*; D007684:Kidney Tubules / Q000276:immunology / Q000473:pathology; D008297:Male; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000276:immunology*; D014517:Ureteral Obstruction / Q000150:complications / Q000276:immunology*
chemical_list: C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D018836:Inflammation Mediators
keywords: B lymphocyte; CC chemokine ligand-2; fibrosis; unilateral ureteral obstruction