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抗核抗体产生的 RP105(-)B 细胞,来自红斑狼疮患者,与正常受试者相比,表现出对 BCMA 的更优先表达,而不是 BAFF-R。

Autoantibody-producing RP105(-) B cells, from patients with systemic lupus erythematosus, showed more preferential expression of BCMA compared with BAFF-R than normal subjects.

机构信息

Division of Rheumatology, Saga University, 5-1-1 Nabeshima, Saga 849-8501, Japan.

出版信息

Rheumatology (Oxford). 2010 Apr;49(4):662-70. doi: 10.1093/rheumatology/kep437. Epub 2010 Jan 22.

Abstract

OBJECTIVE

B cells lacking RP105 produce autoantibodies in patients with SLE. Expression of B-cell activating factor (BAFF) binding receptors (BBRs) and survival of RP105(-) B cells from SLE patients were examined.

METHODS

Detection of difference of gene expression between RP105(-) and RP105(+) B cells was done by DNA microarrays. Surface expression was confirmed by flow cytometry. The contribution of BAFF, a proliferation-inducing ligand (APRIL) and monomers/trimers of sCD40L to survival of RP105(-) and RP105(+) B cells was examined.

RESULTS

Gene expression of B-cell maturation antigen (BCMA) was different among BBRs in RP105(-) and RP105(+) B cells in SLE. Preferential expression of BCMA on RP105(-) B cells was confirmed compared with RP105(+) B cells by flow cytometry, although BAFF receptor (BAFF-R) expression on RP105(-) B cells was significantly lower. Additionally, relative ratios of BCMA/BAFF-R expression on RP105(-) B cells were increased significantly in SLE patients compared with normal subjects. Stimulation by sCD40L decreased the number of surviving RP105(-) and RP105(+) B cells in vitro. RP105(+) B cells were not rescued from sCD40L-induced cell death by BAFF and/or APRIL. In contrast, either BAFF or APRIL maintained the survival of RP105(-) B cells due to avoidance of cell death. Activated RP105(-) B cells reduced BAFF-R and increased BCMA levels.

CONCLUSIONS

RP105(-) B cells from SLE patients showed more preferential expression of BCMA compared with BAFF-R than normal subjects, and were possibly regulated by BAFF/APRIL. Our results provide a new insight of BCMA and their ligands in B cells from SLE patients.

摘要

目的

缺乏 RP105 的 B 细胞会在 SLE 患者中产生自身抗体。本研究检测了 SLE 患者中 B 细胞激活因子(BAFF)结合受体(BBR)的表达和 RP105(-)B 细胞的存活情况。

方法

通过 DNA 微阵列检测 RP105(-)和 RP105(+)B 细胞之间基因表达的差异。通过流式细胞术确认表面表达。检测 BAFF、增殖诱导配体(APRIL)和 sCD40L 单体/三聚体对 RP105(-)和 RP105(+)B 细胞存活的影响。

结果

SLE 患者中 RP105(-)和 RP105(+)B 细胞的 BBR 基因表达不同。通过流式细胞术证实,与 RP105(+)B 细胞相比,RP105(-)B 细胞上 BCMA 的表达更为优先,尽管 RP105(-)B 细胞上 BAFF 受体(BAFF-R)的表达显著降低。此外,与正常受试者相比,SLE 患者中 RP105(-)B 细胞上 BCMA/BAFF-R 的相对比值显著增加。体外刺激 sCD40L 可减少存活的 RP105(-)和 RP105(+)B 细胞数量。BAFF 和/或 APRIL 不能挽救 RP105(+)B 细胞免受 sCD40L 诱导的细胞死亡。相比之下,BAFF 或 APRIL 均可维持 RP105(-)B 细胞的存活,从而避免细胞死亡。激活的 RP105(-)B 细胞降低了 BAFF-R 水平,增加了 BCMA 水平。

结论

与正常受试者相比,SLE 患者的 RP105(-)B 细胞表现出对 BCMA 的表达更优先于 BAFF-R,并且可能受到 BAFF/APRIL 的调节。我们的研究结果为 SLE 患者 B 细胞中 BCMA 及其配体提供了新的见解。

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