CD19 regulates the development of bleomycin-induced pulmonary fibrosis in a mouse model.
OBJECTIVE
The contribution of CD19 and B lymphocytes to pulmonary fibrosis is controversial. The aim of this study was to address the role of CD19 during the development of pulmonary fibrosis.


METHODS
Mice lacking or overexpressing the B cell surface molecule CD19, which is known as a positive regulator of B cell activation, were used in a model of bleomycin-induced pulmonary fibrosis. Ten or sixteen days after intratracheal injection of bleomycin, lung sections from mice were evaluated by histologic analysis. Seven days after instillation, the total leukocyte count and the number of B cells in bronchoalveolar lavage fluid (BALF) were determined, using a hemocytometer and flow cytometry. Bleomycin was also administered into selectin-deficient or intercellular adhesion molecule 1-deficient mouse strains. The level of CXCR3 expression on B cells was determined by flow cytometry.


RESULTS
CD19 deficiency significantly reduced susceptibility to intratracheal bleomycin challenge on day 16, while CD19 overexpression augmented fibrosis even on day 10. Furthermore, the survival rate and number of B cells in BALF also correlated with CD19 expression levels. The accumulation of B cells in BALF was dependent on CD19 levels, whereas there was no association with the levels of selectins or intercellular adhesion molecule 1. Additionally, CXCR3 was up-regulated in BALF B cells, while it was rarely expressed on circulating B cells. Furthermore, CD19 signaling facilitated B cell CXCR3 up-regulation in response to stimulation in vitro.


CONCLUSIONS
These results suggest that CD19 signaling is associated with the development of pulmonary fibrosis by controlling B cell infiltration into lung tissue, which may be associated with CXCR3 up-regulation.
Komura
Kazuhiro
K
Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
Yanaba
Koichi
K
Horikawa
Mayuka
M
Ogawa
Fumihide
F
Fujimoto
Manabu
M
Tedder
Thomas F
TF
Sato
Shinichi
S
D000818:Animals; D018941:Antigens, CD19 / Q000502:physiology*; D001402:B-Lymphocytes; D001761:Bleomycin; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D004195:Disease Models, Animal; D005434:Flow Cytometry; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis; D007958:Leukocyte Count; D051379:Mice; D011658:Pulmonary Fibrosis / Q000139:chemically induced* / Q000473:pathology; D054367:Receptors, CXCR3 / Q000032:analysis; D019087:Selectins / Q000032:analysis; D015854:Up-Regulation
D018941:Antigens, CD19; C515187:CXCR3 protein, human; D054367:Receptors, CXCR3; D019087:Selectins; D001761:Bleomycin; D018799:Intercellular Adhesion Molecule-1