Aberrant B1 cell migration into the thymus results in activation of CD4 T cells through its potent antigen-presenting activity in the development of murine lupus.
B1 cells have different origin and function from conventional B (B2) cells and are considered to be involved in autoantibody production in the development of autoimmune disease. We found that B1 cells preferentially accumulated in the target organs including thymus in aged BWF1 mice, a murine model for systemic lupus erythematosus, and that B lymphocyte chemoattractant (BLC/CXCL13) expression was increased in the thymus before the onset of lupus nephritis, while stromal cell-derived factor-1 (SDF-1/CXCL12) and secondary lymphoid tissue chemokine (SLC/CCL21) expression remained unchanged. Adhesion molecules such as peripheral node addressin (PNAd), ICAM-1, and VCAM-1 were also expressed on endothelial cells in the enlarged thymic perivascular space (PVS) in aged BWF1 mice. BLC protein and PNAd were co-localized on these high-endothelial-venules-like vessels in enlarged PVS. B1 cells expressed higher level of costimulatory molecules and showed a potent antigen-presenting activity in allogeneic mixed lymphocyte reaction comparable to splenic dendritic cells. Interestingly, B1 cells stimulated proliferation of autologous thymic CD4 T cells in the presence of IL-2. These results indicate that aberrant B1 cell trafficking into the thymus due to ectopic high expression of BLC may result in an activation of self-reactive T cells in the development of murine lupus.
Sato
Taku
T
Department of Molecular Preventive Medicine, School of Medicine, University of Tokyo, Tokyo, Japan.
Ishikawa
Sho
S
Akadegawa
Kenji
K
Ito
Toshihiro
T
Yurino
Hideaki
H
Kitabatake
Masahiro
M
Yoneyama
Hiroyuki
H
Matsushima
Kouji
K
D000367:Age Factors; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002465:Cell Movement / Q000276:immunology*; D054382:Chemokine CXCL13; D019743:Chemokines, CXC / Q000378:metabolism; D004195:Disease Models, Animal; D004727:Endothelium / Q000378:metabolism; D007700:Kinetics; D008180:Lupus Erythematosus, Systemic / Q000209:etiology / Q000276:immunology*; D051379:Mice; D018089:Superantigens / Q000276:immunology; D013950:Thymus Gland / Q000276:immunology* / Q000378:metabolism
D015815:Cell Adhesion Molecules; D054382:Chemokine CXCL13; D019743:Chemokines, CXC; C486386:Cxcl13 protein, mouse; D018089:Superantigens