Protective and pathogenic roles for B cells during systemic autoimmunity in NZB/W F1 mice.
Protective and pathogenic roles for B cells during systemic autoimmunity in NZB/W F1 mice.
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DOI：
10.4049/jimmunol.0902391
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发表时间：
2010-05-01
期刊：
影响因子：
--
通讯作者：
Tedder TF
中科院分区：
文献类型：
--
作者：
Haas KM;Watanabe R;Matsushita T;Nakashima H;Ishiura N;Okochi H;Fujimoto M;Tedder TF
在自身免疫性疾病的过程中，描述B淋巴细胞的相对贡献是困难的。因此，在人系统性红斑狼疮模型NZ B/W F1小鼠中比较了使用强效CD 20 mAb耗竭所有成熟B细胞或使用配体阻断CD 22 mAb耗竭循环和边缘区B细胞的效果。单次低剂量mAb处理在NZ B/W F1和C57 BL/6小鼠中有效地耗尽B细胞。在NZ B/W F1小鼠中，通过重复CD 20 mAb治疗预防性B细胞耗竭延长了降植烷加速狼疮的存活期，而CD 22 mAb几乎没有影响。尽管有效的B细胞耗竭，但两种mAb处理均不能阻止自身抗体的产生。此外，与亲本NZ B和NZW品系相比，CD 20、CD 22和对照mAb处理的NZ B/W F1小鼠产生了抗小鼠IgG自身抗体，这可能降低了B细胞耗竭的有效性。尽管如此，在12-28周龄时开始低剂量CD 20 mAb治疗，然后每4周一次显著延迟NZB/W F1小鼠的自发性疾病。相比之下，从4周龄开始的B细胞耗竭加速疾病发作，这导致称为B10细胞的产生IL-10的调节性B细胞亚群的耗竭。B10细胞在NZB/W F1和C57 BL/6小鼠中表型相似，但在年轻的NZB/W F1小鼠中显著扩增。因此，B细胞耗竭对NZ B/W小鼠存活率具有显著影响，这取决于给药开始的时间。因此，不同的B细胞群体在狼疮进展过程中可能具有相反的保护作用和致病作用。
Delineating the relative contributions of B lymphocytes during the course of autoimmune disease has been difficult. Therefore, the effects of depleting all mature B cells using a potent CD20 mAb, or depleting circulating and marginal zone B cells using a ligand-blocking CD22 mAb were compared in NZB/W F1 mice, a model for human systemic lupus erythematosus. Single low-dose mAb treatments depleted B cells efficiently in both NZB/W F1 and C57BL/6 mice. Prophylactic B cell depletion by repeated CD20 mAb treatments prolonged survival during pristane-accelerated lupus in NZB/W F1 mice, while CD22 mAb had little effect. Despite effective B cell depletion, neither mAb treatment prevented autoantibody generation. In addition, CD20, CD22, and control mAb-treated NZB/W F1 mice developed anti-mouse IgG autoantibodies in contrast to parental NZB and NZW strains, which may have reduced the effectiveness of B cell depletion. Despite this, low dose CD20 mAb treatment initiated at 12–28 weeks of age and then every 4 weeks significantly delayed spontaneous disease in NZB/W F1 mice. By contrast, B cell depletion starting at 4 wks of age hastened disease onset, which paralleled depletion of the IL-10-producing regulatory B cell subset called B10 cells. B10 cells were phenotypically similar in NZB/W F1 and C57BL/6 mice, but were expanded significantly in young NZB/W F1 mice. Thus, B cell depletion had significant effects on NZB/W mouse survival that were dependent on the timing of treatment initiation. Thereby, distinct B cell populations may have opposing protective and pathogenic roles during lupus progression.
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DOI：
10.1084/jem.157.1.202
发表时间：
1983-01-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Hayakawa K;Hardy RR;Parks DR;Herzenberg LA
通讯作者：
Herzenberg LA
影响因子：
15.9
作者：
Grammer, AC;Slota, R;Lipsky, PE
通讯作者：
Lipsky, PE
影响因子：
4.4
作者：
Hamaguchi, Y;Uchida, J;Tedder, TF
通讯作者：
Tedder, TF
影响因子：
15.9
作者：
Hu, Chang-Yun;Rodriguez-Pinto, Daniel;Wen, Li
通讯作者：
Wen, Li
影响因子：
6
作者：
Hasegawa, Minoru;Hamaguchi, Yasuhito;Tedder, Thomas F.
通讯作者：
Tedder, Thomas F.