B-cell depletion inhibits arthritis in a collagen-induced arthritis (CIA) model, but does not adversely affect humoral responses in a respiratory syncytial virus (RSV) vaccination model
B-cell depletion inhibits arthritis in a collagen-induced arthritis (CIA) model, but does not adversely affect humoral responses in a respiratory syncytial virus (RSV) vaccination model
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DOI：
10.1182/blood-2004-11-4547
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发表时间：
2005-10-01
期刊：
影响因子：
20.3
通讯作者：
Collins, M
中科院分区：
文献类型：
--
作者：
Dunussi-Joannopoulos, K;Hancock, GE;Collins, M
我们报道了一种小鼠B细胞耗竭免疫偶联物（与calicheamicin偶联的抗CD22单克隆抗体[mAb]）的开发，并在体内使用它来表征小鼠原发性和继发性淋巴组织中CD22(+) B细胞耗竭和重建的动力学。在小鼠胶原诱导关节炎（CIA）模型和呼吸道合胞病毒（RSV）疫苗接种模型中进一步研究了b细胞耗竭的作用。结果表明：(1)免疫偶联物具有b细胞特异性体外和体内细胞毒性；(2)骨髓和脾脏的b细胞重构开始于衰竭后第30天左右，到第50天所有组织都完成了b细胞重构；(3)在CIA模型中，b细胞耗竭抑制临床和组织学关节炎的发展；(4) II型胶原抗体水平的降低对CIA的临床和组织学预防不是必需的；(5)在RSV疫苗模型中，b细胞耗竭不会对攻击后的记忆抗体反应产生不利影响，也不会对肺部感染病毒的清除产生不利影响。这些结果首次证明，只有b细胞减少而不是II型胶原抗体水平与关节炎的预防相关，并代表了cd22靶向b细胞消耗在小鼠自身免疫和疫苗接种模型中的作用的关键见解。
We report the development of a mouse B cell-depleting immunoconjugate (anti-CD22 monoclonal antibody [mAb] conjugated to calicheamicin) and its in vivo use to characterize the kinetics of CD22(+) B-cell depletion and reconstitution in murine primary and secondary lymphoid tissues. The effect of B-cell depletion was further studied in a murine collagen-induced arthritis (CIA) model and a respiratory syncytial virus (RSV) vaccination model. Our results show that (1) the immunoconjugate has B-cell-specific in vitro and in vivo cytotoxicity; (2) B-cell reconstitution starts in the bone marrow and spleen around day 30 after depletion and is completed in all tissues tested by day 50; (3) B-cell depletion inhibits the development of clinical and histologic arthritis in the CIA model; (4) depletion of type II collagen antibody levels is not necessary for clinical and histologic prevention of CIA; and (5) B-cell depletion does not adversely affect memory antibody responses after challenge nor clearance of infectious virus from lungs in the RSV vaccination model. These results demonstrate for the first time that only B-cell reduction but not type II collagen antibody levels correlate with the prevention of arthritis and represent key insights into the role of CD22-targeted B-cell depletion in mouse autoimmunity and vaccination models.