Japanese Journal of Clinical Immunology
Online ISSN : 1349-7413
Print ISSN : 0911-4300
ISSN-L : 0911-4300
Review Articles
Molecular mechanisms of B lymphocyte depletion by CD20 immunotherapy
Yasuhito HAMAGUCHI
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2009 Volume 32 Issue 1 Pages 29-34

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Abstract

  Anti-CD20 antibody immunotherapy effectively treats non-Hodgkin's lymphoma and autoimmune disease. However, the cellular and molecular pathways for B cell depletion remain undefined and the in vivo effect of immunotherapy on tissue B cells and their subsets is generally unknown. To identify the mechanisms for B cell depletion in vivo, a new mouse model for anti-CD20 immunotherapy was developed using a panel of twelve mouse anti-mouse CD20 monoclonal antibodies. Anti-CD20 antibodies rapidly depleted the vast majority of circulating and tissue B cells in an isotype-restricted manner that was completely dependent on effector cell Fc receptor expression. B cell depletion utilized FcγRI-, FcγRIII- and FcγRIV-dependent pathways, while B cells were not eliminated in FcR common γ chain-deficient mice. Monocytes were the dominant effector cells for B cell depletion, with no demonstrable role for T or NK cells. Although most anti-CD20 antibodies activated complement in vitro, B cell depletion was completely effective in mice with genetic deficiencies in C3 complement components. The considerable factors that determine the effectiveness of anti-CD20 immunotherapy are following: the expression level of CD20 on B cell surface; the dosage of anti-CD20 mAb; the association of Fcγ receptor with the isotype of the antibies; B cell subpopulations within different tissues. These findings have important clinical implications for anti-CD20 and other antibody-based therapies.

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© 2009 The Japan Society for Clinical Immunology
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