A unique form of haptoglobin produced by murine hematopoietic cells supports B-cell survival, differentiation and immune response.
A unique form of haptoglobin produced by murine hematopoietic cells supports B-cell survival, differentiation and immune response.
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鼠造血细胞产生的一种独特形式的抗果糖蛋白支持B细胞存活，分化和免疫反应。
DOI：
10.1016/j.molimm.2013.03.008
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发表时间：
2013-10
影响因子：
3.6
通讯作者：
Baumann H
中科院分区：
文献类型：
--
作者：
Huntoon KM;Russell L;Tracy E;Barbour KW;Li Q;Shrikant PA;Berger FG;Garrett-Sinha LA;Baumann H
结合珠蛋白（Hp）是一种急性时相反应物和主要的血红蛋白结合蛋白，在宿主免疫中具有独特的作用。以前，我们证明了Hp缺陷的C57 BL/6 J小鼠表现出发育迟缓的成熟T细胞和B细胞，导致抗原特异性IgG水平显着降低。目前的研究确定了白细胞衍生的原Hp作为最佳免疫应答的相关介质。用Hp+/+骨髓重建Hp−/−小鼠恢复了对卵清蛋白的正常免疫应答。此外，将来自B细胞缺陷型和Hp缺陷型小鼠的骨髓混合物移植到Rag 1 −/−/ Hp+/+受体中，导致小鼠具有与Hp−/−小鼠相似的免疫反应缺陷。这表明B细胞区室而不是肝脏产生的Hp在功能上有助于正常的免疫反应。从脾分离的白细胞表达Hp并释放非蛋白水解加工的Hp原，其与肝源性Hp的独特不同在于不与血红蛋白结合。虽然添加纯化的血浆Hp培养的B细胞没有改变反应，亲Hp分离脾细胞增强细胞增殖和生产的IgG。总的来说，野生型和Hp缺陷小鼠的比较表明，淋巴细胞来源的Hp，包括B细胞本身产生的Hp，支持体内生存和功能分化的B细胞，以确保最佳的免疫应答的新的调节活性。
Haptoglobin (Hp), an acute phase reactant and major hemoglobin-binding protein, has a unique role in host immunity. Previously, we demonstrated that Hp-deficient C57BL/6J mice exhibit stunted development of mature T- and B-cells resulting in markedly lower levels of antigen-specific IgG. The current study identified leukocyte-derived pro-Hp as a relevant mediator of an optimal immune response. Reconstitution of Hp−/− mice with Hp+/+ bone marrow restored normal immune response to ovalbumin. Furthermore, transplanting a mixture of bone marrow-derived from B-cell-deficient and Hp-deficient mice into Rag1−/−/ Hp+/+ recipients resulted in mice with a defective immune response similar to Hp−/− mice. This suggests that Hp generated by the B-cell compartment, rather than by the liver, is functionally contributing to a normal immune response. Leukocytes isolated from the spleen express Hp and release a non-proteolytically processed pro-Hp that uniquely differed from liver-derived Hp by not binding to hemoglobin. While addition of purified plasma Hp to cultured B-cells did not alter responses, pro-Hp isolated from splenocytes enhanced cellular proliferation and production of IgG. Collectively, the comparison of wild-type and Hp-deficient mice suggests a novel regulatory activity for lymphocyte-derived Hp, including Hp produced by B-cells themselves, that supports in vivo survival and functional differentiation of the B-cells to ensure an optimal immune response.
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