Defective B1 cell homing to the peritoneal cavity and preferential recruitment of B1 cells in the target organs in a murine model for systemic lupus erythematosus.
We previously reported that B lymphocyte chemoattractant (BLC; CXCL13) was highly and ectopically expressed in aged (NZB x NZW)F1 (BWF1) mice developing lupus nephritis, and that B1 cells were preferentially chemoattracted toward BLC. We demonstrate in this study that B1 cells fail to home to the peritoneal cavity in aged BWF1 mice developing lupus nephritis, and that they are preferentially recruited to the target organs including the kidney, lung, and thymus when injected i.v. In contrast, B1 cells homed to the peritoneal cavity in aged BALB/c mice as effectively as in young mice. Accumulation of B1 cells to the omentum milky spots was also impaired in aged BWF1 mice compared with young mice. CD11bhighF4/80high cells with macrophage morphology were confirmed to be a major cell source for BLC in the peritoneal cavity both in young and aged BWF1 mice. However, the number of BLC-producing peritoneal macrophages was markedly decreased in aged BWF1 mice. These results suggest that the decreased number of BLC-producing peritoneal macrophages together with ectopic high expression of BLC in aged BWF1 mice result in abnormal B1 cell trafficking during the development of murine lupus.
Department of Molecular Preventive Medicine, School of Medicine, University of Tokyo, Tokyo, Japan.
Toshihiro
T
Ito
Sho
S
Ishikawa
Taku
T
Sato
Kenji
K
Akadegawa
Hideaki
H
Yurino
Masahiro
M
Kitabatake
Shigeto
S
Hontsu
Taichi
T
Ezaki
Hiroshi
H
Kimura
Kouji
K
Matsushima
D000375:Aging / Q000276:immunology / Q000473:pathology; D000818:Animals; D016175:B-Lymphocyte Subsets / Q000378:metabolism / Q000473:pathology* / Q000637:transplantation; D002452:Cell Count; D002465:Cell Movement / Q000276:immunology*; D054382:Chemokine CXCL13; D019743:Chemokines, CXC / Q000096:biosynthesis; D003433:Crosses, Genetic; D004195:Disease Models, Animal; D005260:Female; D008180:Lupus Erythematosus, Systemic / Q000276:immunology* / Q000473:pathology*; D008181:Lupus Nephritis / Q000276:immunology / Q000473:pathology; D017737:Macrophages, Peritoneal / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008814:Mice, Inbred NZB; D009928:Organ Specificity / Q000276:immunology; D010529:Peritoneal Cavity / Q000166:cytology / Q000473:pathology*
D054382:Chemokine CXCL13; D019743:Chemokines, CXC; C486386:Cxcl13 protein, mouse