@article{oai:kanazawa-u.repo.nii.ac.jp:00013575,
 author = {濱口, 儒人},
 issue = {1},
 journal = {日本臨床免疫学会会誌 = Japanese Journal of Clinical Immunology},
 month = {Jan},
 note = {CD20はB細胞に特異的に発現している膜表面分子であり，抗ヒトCD20ヒト・マウスキメラ抗体（リツキシマブ）はB細胞由来悪性リンパ腫に有効性が示されている．また，近年B細胞の自己免疫疾患，炎症性疾患への関与を示唆する報告が相次ぎ，B細胞が治療ターゲットとして注目を集めていることから，CD20抗体療法はこれらの疾患へも応用が試みられている．しかしながら，抗CD20抗体が生体内でB細胞を除去する分子機構は充分に解明されていなかった．このため，筆者らはマウス抗マウスCD20モノクローナル抗体を作成し検討を重ねてきた．その結果，抗CD20抗体がB細胞を除去する分子機構は，マクロファージをエフェクター細胞とし，Fcγレセプターを介した抗体依存性細胞障害活性が主要な経路であることが明らかとなった．また，CD20抗体療法の効果を規定する因子として，①細胞表面に発現しているCD20の発現量，②投与する抗体量，③抗体のアイソタイプ（サブクラス），④B細胞亜集団，⑤解剖学的部位などが重要であると考えられた．さらに，治療抵抗性のB細胞に対し，局所にマクロファージを動員することで除去の効率を上げることができた．これらの知見は，CD20抗体療法の治療効果を高める上で重要と考えられた． 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.},
 pages = {29--34},
 title = {抗CD20抗体がB細胞を除去する分子機構について},
 volume = {32},
 year = {2009}
}