Importance of cellular microenvironment and circulatory dynamics in B cell immunotherapy.

Abstract

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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@article{Gong2005ImportanceOC, title={Importance of cellular microenvironment and circulatory dynamics in B cell immunotherapy.}, author={Qian Gong and Qinglin Ou and Shiming Ye and Wyne P Lee and Jennine Cornelius and Lauri J Diehl and Lea Weinisch and Zhilan Hu and Yanmei Lu and Yongmei Chen and Yan Wu and Yu-Ju Gloria Meng and Peter Gribling and Zhonghua Lin and Kathy Dang Nguyen and Thanhvien Tran and Yifan Zhang and Hugh Rosen and Flavius Martin and Andrew Chan}, journal={Journal of immunology}, year={2005}, volume={174 2}, pages={817-26} }