Lee Nam-Sihk, Barber Laura, Akula Shaw M, Sigounas George, Kataria Yash P, Arce Sergio
Division of Pulmonary, Critical Care and Sleep Medicine, Brody School of Medicine, East Carolina University, Greenville, NC 27834, USA.
Clin Vaccine Immunol. 2011 Aug;18(8):1306-16. doi: 10.1128/CVI.05118-11. Epub 2011 Jun 8.
The presence of hypergammaglobulinemia, autoantibodies, and circulating immune complexes suggests that humoral immunity may contribute to the pathogenesis of sarcoidosis. However, little is known about the role played by B cells in the development of this disease. Here we investigated the subpopulation distribution, response to stimulation, and levels of the nuclear transcription factor NF-κB/p65 in peripheral blood B cells from patients with severe chronic sarcoidosis. Patients with severe chronic sarcoidosis had absolute B-cell lymphopenia and exhibited significantly decreased frequencies and total numbers of memory (CD19(+) CD27(+)) B cells. The reduced numbers of memory B cells in these patients reflected a decrease in the total numbers of class-switched (CD19(+) CD27(+) IgD(-)) and unswitched (CD19(+) CD27(+) IgD(+)) memory B cells and coincided with an increased frequency of circulating (CD19(+/-) CD20(-) CD27(++)) plasmablasts. Polyclonal stimulation of sarcoid B cells resulted in reduced expression of activation markers (i.e., CD25, CD69, and CD86), decreased proliferation, and impaired plasma cell differentiation. Baseline expression of p65 in B cells was reduced in 65% of the patients. These results suggest disturbed homeostasis, intrinsic signaling defects, and anergy within the peripheral B-cell compartments of patients with severe chronic sarcoidosis.
高球蛋白血症、自身抗体和循环免疫复合物的存在表明体液免疫可能参与结节病的发病机制。然而，关于B细胞在该疾病发展中所起的作用知之甚少。在此，我们研究了重度慢性结节病患者外周血B细胞的亚群分布、对刺激的反应以及核转录因子NF-κB/p65的水平。重度慢性结节病患者存在绝对B细胞淋巴细胞减少，且记忆（CD19(+) CD27(+)）B细胞的频率和总数显著降低。这些患者记忆B细胞数量减少反映了类别转换（CD19(+) CD27(+) IgD(-)）和未转换（CD19(+) CD27(+) IgD(+)）记忆B细胞总数的减少，同时循环（CD19(+/-) CD20(-) CD27(++)）浆母细胞的频率增加。结节病B细胞的多克隆刺激导致激活标志物（即CD25、CD69和CD86）表达降低、增殖减少以及浆细胞分化受损。65%的患者B细胞中p65的基线表达降低。这些结果提示重度慢性结节病患者外周B细胞区室存在内环境稳态紊乱、内在信号缺陷和无反应性。
