Importance of cellular microenvironment and circulatory dynamics in B cell immunotherapy

Qian Gong, Qinglin Ou, Shiming Ye, Wyne P. Lee, Jennine Ochoa, Lauri Diehl, Yu Lin Wei, Zhilan Hu, Yanmei Lu, Yongmei Chen, Yan Wu, Y. Gloria Meng, Peter Gribling, Zhonghua Lin, Kathy Nguyen, Thanhvien Tran, Yifan Zhang, Hugh Rosen, Flavius Martin, Andrew C. Chan

Research output: Contribution to journalArticle

399 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)817-826
Number of pages10
JournalJournal of Immunology
Volume174
Issue number2
DOIs
StatePublished - Jan 15 2005
Externally publishedYes

ASJC Scopus subject areas

  • Immunology

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  • Cite this

    Gong, Q., Ou, Q., Ye, S., Lee, W. P., Ochoa, J., Diehl, L., Wei, Y. L., Hu, Z., Lu, Y., Chen, Y., Wu, Y., Meng, Y. G., Gribling, P., Lin, Z., Nguyen, K., Tran, T., Zhang, Y., Rosen, H., Martin, F., & Chan, A. C. (2005). Importance of cellular microenvironment and circulatory dynamics in B cell immunotherapy. Journal of Immunology, 174(2), 817-826. https://doi.org/10.4049/jimmunol.174.2.817