B cell-derived vascular endothelial growth factor A promotes lymphangiogenesis and high endothelial venule expansion in lymph nodes

• Published in: The Journal of immunology (1950) Vol. 184; no. 9; pp. 4819 - 4826
• Main Authors: Shrestha, Binita, Hashiguchi, Teruto, Ito, Takashi, Miura, Naoki, Takenouchi, Kazunori, Oyama, Yoko, Kawahara, Ko-Ichi, Tancharoen, Salunya, Ki-I, Yuya, Arimura, Noboru, Yoshinaga, Narimasa, Noma, Satoshi, Shrestha, Chandan, Nitanda, Takao, Kitajima, Shinichi, Arimura, Kimiyoshi, Sato, Masahiro, Sakamoto, Taiji, Maruyama, Ikuro
• Format: Journal Article
• Language: English
• Published: United States 01-05-2010
• Subjects: Adaptive Immunity - genetics; Animals; Antibody Formation - genetics; Antigens, CD19 - biosynthesis; Antigens, CD19 - genetics; B-Lymphocytes - immunology; B-Lymphocytes - metabolism; Down-Regulation - genetics; Down-Regulation - immunology; Endothelium, Lymphatic - immunology; Endothelium, Lymphatic - metabolism; Endothelium, Lymphatic - pathology; Humans; Immune Tolerance - genetics; Inflammation Mediators - antagonists & inhibitors; Inflammation Mediators - physiology; Lymph Nodes - immunology; Lymph Nodes - metabolism; Lymph Nodes - pathology; Lymphangiogenesis - genetics; Lymphangiogenesis - immunology; Mice; Mice, Inbred C57BL; Mice, Transgenic; Ovalbumin - administration & dosage; Ovalbumin - antagonists & inhibitors; Ovalbumin - immunology; Spleen - immunology; Spleen - metabolism; Spleen - pathology; Vascular Endothelial Growth Factor A - biosynthesis; Vascular Endothelial Growth Factor A - genetics; Vascular Endothelial Growth Factor A - physiology; Venules - immunology; Venules - metabolism; Venules - pathology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.0903063

Vascular endothelial growth factor A (VEGF-A) is a prominent growth factor for both angiogenesis and lymphangiogenesis. Recent studies have shown the importance of VEGF-A in enhancing the growth of lymphatic endothelial cells in lymph nodes (LNs) and the migration of dendritic cells into LNs. VEGF-A is produced in inflamed tissues and/or in draining LNs, where B cells are a possible source of this growth factor. To study the effect of B cell-derived VEGF-A, we created transgenic mice (CD19(Cre)/hVEGF-A(fl)) that express human VEGF-A specifically in B cells. We found that the human VEGF-A produced by B cells not only induced lymphangiogenesis in LNs, but also induced the expansion of LNs and the development of high endothelial venules. Contrary to our expectation, we observed a significant decrease in the Ag-specific Ab production postimmunization with OVA and in the proinflammatory cytokine production postinoculation with LPS in these mice. Our findings suggest immunomodulatory effects of VEGF-A: B cell-derived VEGF-A promotes both lymphangiogenesis and angiogenesis within LNs, but then suppresses certain aspects of the ensuing immune responses.