Nurse-like cells from bone marrow and synovium of patients with rheumatoid arthritis promote survival and enhance function of human B cells
Nurse-like cells from bone marrow and synovium of patients with rheumatoid arthritis promote survival and enhance function of human B cells
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DOI：
10.1172/jci3162
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发表时间：
1998-08-01
影响因子：
15.9
通讯作者：
Lipsky, PE
中科院分区：
文献类型：
--
作者：
Shimaoka, Y;Attrep, JF;Lipsky, PE
已知胸腺滋养细胞与T细胞相互作用，并在其功能成熟中发挥作用。然而，滋养细胞在B细胞成熟和分化中的作用还不太明确，特别是在淋巴结外部位。为了解决这个问题，从RA患者的骨髓和滑膜组织（RA-NLC）的护士样细胞克隆建立和表征。RA-NLC组成型表达CD 29、CD 49 c、CD 54（ICAM-1）、CD 106（VCAM-1）、CD 157（BST-1）和I类MHC分子，并分泌IL-6、IL-7、IL-8、粒细胞-巨噬细胞集落刺激因子（GM-CSF）和粒细胞集落刺激因子（G-CSF）。骨髓源性和滑膜RA-NLC的不同之处在于，前者分泌IL-7，并表达更高密度的CD 157组成性和IFN γ刺激后，而后者分泌G-CSF和更多的IL-6。骨髓和滑膜RA-NLC的刺激诱导CD 40和II类MHC的表达，但不诱导CD 154（CD 40 L）或CD 35的表达。RA-NLC可使外周血B细胞免于自发凋亡，并促进B细胞存活> 4 wk。B细胞存活被抗CD 106或CD 157的抗体阻断。RA-NLC还增加了B细胞的IG产生。在与RA-NLC长期培养（4-6周）后，观察到B细胞的长出，但单独培养或与成纤维细胞培养均未观察到。尽管RA-NLC本身没有被EBV感染，但从这些培养物衍生的所有B细胞系都已被EBV转化。前体频率分析表明，在与RA-NLC共培养时，12，500个外周B细胞中约有1个可以产生这些EBV转化的B细胞系。这些结果表明，来自骨髓和滑膜的RA-NLC具有拯救B细胞免于自发凋亡、促进IG产生和促进EBV转化的B淋巴母细胞样细胞生长的能力。这些发现表明，RA-NLC可能在局部和全身的B细胞的高反应性类风湿性关节炎的特点发挥作用。
Thymic nurse cells are known to interact with T cells and play a role in their functional maturation. However, the role of nurse cells in B cell maturation and differentiation is less well established, especially at extralymphoid sites. To address this issue, nurse-like cell clones from bone marrow and synovial tissue of patients with RA (RA-NLC) were established and characterized. RA-NLC constitutively expressed CD29, CD49c, CD54 (ICAM-1), CD106 (VCAM-1), CD157 (BST-1), and class I MHC molecules, and secreted IL-6, IL-7, IL-8, granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF). Bone marrow-derived and synovial RA-NLC differed in that the former secreted IL-7 and expressed a greater density of CD157 constitutively and after stimulation with IFN gamma, whereas the latter secreted G-CSF and more IL-6. Stimulation of both bone marrow and synovial RA-NLC induced expression of CD40 and class II MHC, but not CD154 (CD40L) or CD35. RA-NLC rescued peripheral B cells from spontaneous apoptosis and promoted survival of B cells for > 4 wk. B cell survival was blocked by antibodies to CD106 or CD157. RA-NLC also increased Ig production from B cells. After long-term culture (4-6 wk) with RA-NLC, but not alone or with fibroblasts, outgrowth of B cells was observed. All B cell lines derived from these cultures had been transformed by EBV, although the RA-NLC themselves were not infected with EBV, Precursor frequency analysis indicated that similar to 1 in 12,500 peripheral B cells could give rise to these EBV-transformed B cell lines upon coculture with RA-NLC. These results indicate that RA-NLC from bone marrow and synovium have the capacity to rescue B cells from spontaneous apoptosis, facilitate Ig production, and promote the outgrowth of EBV-transformed B lymphoblastoid cells. These findings suggest that RA-NLC may play a role in the local and systemic hyperreactivity of B cells characteristic of rheumatoid arthritis.