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Gong, Qian; Ou, Qinglin; Ye, Shiming; Lee, Wyne P; Cornelius, Jennine; Diehl, Lauri; Lin, Wei Yu; Hu, Zhilan; Lu, Yanmei; Chen, Yongmei; Wu, Yan; Meng, Y. Gloria; Gribling, Peter; Lin, Zhonghua; Nguyen, Kathy; Tran, Thanhvien; Zhang, Yifan; Rosen, Hugh; Martin, Flavius; Chan, Andrew C
The Journal of immunology (1950), 01/2005, Volume: 174, Issue: 2Journal Article
B cell immunotherapy has emerged as a mainstay in the treatment of lymphomas and autoimmune diseases. Although the microenvironment has recently been demonstrated to play critical roles in B cell homeostasis, its contribution to immunotherapy is unknown. To analyze the in vivo factors that regulate mechanisms involved in B cell immunotherapy, we used a murine model for human CD20 (hCD20) expression in which treatment of hCD20(+) mice with anti-hCD20 mAbs mimics B cell depletion observed in humans. We demonstrate in this study that factors derived from the microenvironment, including signals from the B cell-activating factor belonging to the TNF family/BLyS survival factor, integrin-regulated homeostasis, and circulatory dynamics of B cells define distinct in vivo mechanism(s) and sensitivities of cells in anti-hCD20 mAb-directed therapies. These findings provide new insights into the mechanisms of immunotherapy and define new opportunities in the treatment of cancers and autoimmune diseases.
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