A novel function of B lymphocytes from normal mice to suppress autoimmunity in (NZB x NZW)F1 mice
A novel function of B lymphocytes from normal mice to suppress autoimmunity in (NZB x NZW)F1 mice
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DOI：
10.1046/j.1365-2567.2000.00005.x
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发表时间：
2000-05-01
期刊：
影响因子：
6.4
通讯作者：
Hamaoka, T
中科院分区：
文献类型：
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作者：
Ono, S;Shao, DZ;Hamaoka, T
在易发生全身性自身免疫的 (NZB x NZW)F-1 (NZB/WF-1) 小鼠中，以伴随自身抗体的高丙种球蛋白血症为特征的 B 细胞异常被认为是该疾病的主要原因。为了检查 B 细胞在疾病表现中可能的调节作用，我们通过静脉注射 (i.v.) 将正常或自身免疫 B 细胞注射到未受辐射的 NZB/W F-1 小鼠中。注射来自主要组织相容性（MHC）匹配或同种异体正常小鼠的脾B细胞导致自身抗体的血清免疫球蛋白G（IgG）水平显着降低，延迟蛋白尿的出现并延长寿命，而用来自NZB/W F-1或X连锁免疫缺陷（Xid）小鼠的脾B细胞治疗未能抑制自身免疫。此外，体外多克隆抗体对来自治疗小鼠的NZB/WF-1衍生B细胞的脂多糖(LPS)的反应显着降低。有趣的是，NZB/WF-1小鼠在16、18和20周龄或20、22和24周龄时的治疗比在6、8和10周龄时更有效。该治疗还抑制了表面 IgG(+) (sIgG(+)) B 细胞的发育和脾肿大，这在老年 NZB/WF-1 小鼠中尤为突出。此外，当未处理的NZB/W F-1反应B细胞与正常B细胞在体外预培养3天时，它们也减少了随后LPS刺激的自身抗体产生。因此，目前的结果表明正常 B 细胞具有通过纠正 B 细胞异常来改善 NZB/WF-1 小鼠自身免疫性疾病的新功能，并表明 NZB/WF-1 和 Xid 小鼠在这种调节 B 细胞功能方面存在缺陷。
In systemic autoimmune-prone (NZB x NZW)F-1 (NZB/W F-1) mice, B-cell abnormalities characterized by hypergammaglobulinaemia accompanying autoantibodies have been thought to be a main cause of the disease. To examine a possible regulatory role of B cells in the disease manifestations, we injected, intravenously (i.v.), normal or autoimmune B cells into non-irradiated NZB/W F-1 mice. The injection of splenic B cells from major histocompatibility (MHC)-matched or allogeneic normal mice caused a marked decrease in serum immunoglobulin G (IgG) levels of autoantibodies, delayed the appearance of proteinuria and prolonged life span, whereas treatment with splenic B cells from NZB/W F-1 or X-linked immunodeficient (Xid) mice failed to suppress the autoimmunity. Moreover, in vitro polyclonal antibody responses to lipopolysaccharide (LPS) of NZB/W F-1-derived B cells from the treated mice were markedly reduced. Interestingly, the treatment of NZB/W F-1 mice at 16, 18 and 20 or at 20, 22 and 24 weeks of age was more effective than that at 6, 8 and 10 weeks. The treatment also inhibited the development of surface IgG(+) (sIgG(+)) B cells and splenomegaly, prominent in aged NZB/W F-1 mice. In addition, when untreated NZB/W F-1 responding B cells were precultured with normal B cells in vitro for 3 days, they also diminished the autoantibody production to subsequent LPS stimulation. Hence, the present results imply a novel function of normal B cells to ameliorate autoimmune disease in NZB/W F-1 mice by correcting their B-cell abnormalities, and indicate that NZB/W F-1 and Xid mice possess defects in this regulatory B-cell function.