Importance of cellular microenvironment and circulatory dynamics in B cell immunotherapy

J Immunol. 2005 Jan 15;174(2):817-26. doi: 10.4049/jimmunol.174.2.817.

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antibodies, Monoclonal / administration & dosage
  • Antibodies, Monoclonal / blood
  • Antigens, CD20 / blood
  • Antigens, CD20 / genetics
  • Antigens, CD20 / immunology
  • B-Lymphocyte Subsets / cytology*
  • B-Lymphocyte Subsets / immunology*
  • B-Lymphocyte Subsets / metabolism
  • Binding Sites, Antibody
  • Cell Survival / genetics
  • Cell Survival / immunology
  • Complement System Proteins / physiology
  • Disease Susceptibility / immunology
  • Humans
  • Immunization, Passive / methods*
  • Liver / cytology
  • Liver / immunology
  • Lymphocyte Depletion / methods*
  • Mice
  • Mice, Transgenic
  • Microcirculation / cytology
  • Microcirculation / immunology
  • Mononuclear Phagocyte System / cytology
  • Mononuclear Phagocyte System / immunology
  • Spleen / cytology
  • Spleen / immunology

Substances

  • Antibodies, Monoclonal
  • Antigens, CD20
  • Complement System Proteins