The development and function of regulatory B cells expressing IL-10 (B10 cells) requires antigen receptor diversity and TLR signals.
The development and function of regulatory B cells expressing IL-10 (B10 cells) requires antigen receptor diversity and TLR signals.
复制标题
DOI：
10.4049/jimmunol.0900270
复制
发表时间：
2009-06-15
期刊：
影响因子：
--
通讯作者：
Tedder TF
中科院分区：
文献类型：
--
作者：
Yanaba K;Bouaziz JD;Matsushita T;Tsubata T;Tedder TF
自身免疫和炎症部分由调节性 B 细胞控制，包括最近发现的具有 IL-10 活性的 CD1dhiCD5+ B 细胞亚群，称为 B10 细胞，占成年小鼠脾 B 细胞的 1-3%。在这项研究中，确定了影响 B10 细胞生成和 IL-10 产生的途径，并与之前描述的调节性 B 细胞进行了比较。成人脾脏中具有 IL-10 能力的 B 细胞主要为 CD1dhiCD5+，是 IL-10 的主要来源，但不是其他细胞因子。 B10 细胞体内发育和/或成熟需要 Ag 受体多样性和完整的信号通路，但不需要 T 细胞、肠道相关菌群或环境病原体。在老年小鼠和易患自身免疫的小鼠中，脾 B10 细胞频率显着增加，但在对外源性自身抗原诱导的自身免疫敏感的小鼠品系中，脾 B10 细胞频率显着降低。 LPS、PMA加离子霉素体外刺激5 h诱导B10细胞表达胞质IL-10。然而，延长 LPS 或 CD40 刺激（48 小时）在 PMA+离子霉素刺激后诱导额外的成人脾 CD1dhiCD5+ B 细胞表达 IL-10。新生儿脾脏和成人血液或淋巴结 CD1dlo 和/或 CD5− B 细胞的长期 LPS 或 CD40 刺激也会诱导稀有 B 细胞的细胞质 IL-10 能力，CD40 连接一致诱导 CD5 表达。 IL-10 分泌是由 LPS 信号通过 MyD88 依赖性途径诱导的，但在 CD40 连接后不诱导。与其他脾脏 B 细胞相比，LPS 刺激还诱导 B10 细胞快速克隆扩增。因此，适应性信号和先天信号均可调节 B10 细胞的发育、成熟、CD5 表达和 IL-10 产生能力。
Autoimmunity and inflammation are controlled in part by regulatory B cells, including a recently identified IL-10-competent CD1dhiCD5+ B cell subset termed B10 cells that represents 1–3% of adult mouse spleen B cells. In this study, pathways that influence B10 cell generation and IL-10 production were identified and compared with previously described regulatory B cells. IL-10-competent B cells were predominantly CD1dhiCD5+ in adult spleen and were the prevalent source of IL-10 but not other cytokines. B10 cell development and/or maturation in vivo required Ag receptor diversity and intact signaling pathways, but not T cells, gut-associated flora, or environmental pathogens. Spleen B10 cell frequencies were significantly expanded in aged mice and mice predisposed to autoimmunity, but were significantly decreased in mouse strains that are susceptible to exogenous autoantigen-induced autoimmunity. LPS, PMA, plus ionomycin stimulation in vitro for 5 h induced B10 cells to express cytoplasmic IL-10. However, prolonged LPS or CD40 stimulation (48 h) induced additional adult spleen CD1dhiCD5+ B cells to express IL-10 following PMA+ionomycin stimulation. Prolonged LPS or CD40 stimulation of newborn spleen and adult blood or lymph node CD1dlo and/or CD5− B cells also induced cytoplasmic IL-10 competence in rare B cells, with CD40 ligation uniformly inducing CD5 expression. IL-10 secretion was induced by LPS signaling through MyD88-dependent pathways, but not following CD40 ligation. LPS stimulation also induced rapid B10 cell clonal expansion when compared with other spleen B cells. Thereby, both adaptive and innate signals regulate B10 cell development, maturation, CD5 expression, and competence for IL-10 production.
登录
查看更多内容
影响因子：
4.4
作者：
Lampropoulou, Vicky;Hoehlig, Kai;Fillatreau, Simon
通讯作者：
Fillatreau, Simon
影响因子：
4.4
作者：
Higuchi, T;Aiba, Y;Tsubata, T
通讯作者：
Tsubata, T
影响因子：
32.4
作者：
Haas, KM;Hasegawa, M;Tedder, TF
通讯作者：
Tedder, TF
影响因子：
4.4
作者：
Evans, Jamie G.;Chavez-Rueda, Karina A.;Mauri, Claudia
通讯作者：
Mauri, Claudia
影响因子：
4.4
作者：
Hussain, Shabbir;Delovitch, Terry L.
通讯作者：
Delovitch, Terry L.