Harp Christopher T, Lovett-Racke Amy E, Racke Michael K, Frohman Elliot M, Monson Nancy L
Department of Neurology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Clin Immunol. 2008 Sep;128(3):382-91. doi: 10.1016/j.clim.2008.05.002. Epub 2008 Jul 2.
The role of B cells in the pathogenesis of Multiple Sclerosis (MS) is incompletely understood. Here we define a possible role for B cells as myelin-specific antigen presenting cells (B-APCs) in MS. Peripheral blood B cells (PBBC) isolated from both MS patients and healthy controls (HC) were activated in vitro with either CD40L/IL-4 or a Class B CpG oligodeoxynucleotide (CpG ODN)/IL-2. Both activation techniques induced PBBCs to upregulate CD80 and HLA-DR, rendering them more efficient APCs than resting B cells. Although the CD40L/IL-4 B-APCs were highly effective in eliciting CNS-antigen specific proliferation by autologous T cells, CpG ODN/IL-2 stimulated B cells were not. Furthermore, CD40L/IL-4 B-APC induced responses by autologous CD4(+) T cells were susceptible to blocking with anti-HLA-DR antibody, suggesting that T cell responses were specific for antigen presentation by B-APC. CNS-antigen specific CD8(+) T cell proliferation was also blocked by HLA-DR, suggesting that CD8(+) proliferation is in part dependent on CD4(+) help.
B细胞在多发性硬化症（MS）发病机制中的作用尚未完全明确。在此，我们确定了B细胞作为MS中髓鞘特异性抗原呈递细胞（B-APC）的一种可能作用。从MS患者和健康对照（HC）中分离出的外周血B细胞（PBBC），在体外分别用CD40L/IL-4或B类CpG寡脱氧核苷酸（CpG ODN）/IL-2进行激活。这两种激活技术均诱导PBBC上调CD80和HLA-DR，使其比静息B细胞更有效地成为抗原呈递细胞。尽管CD40L/IL-4 B-APC在引发自体T细胞的中枢神经系统抗原特异性增殖方面非常有效，但CpG ODN/IL-2刺激的B细胞则不然。此外，CD40L/IL-4 B-APC诱导的自体CD4(+) T细胞反应易被抗HLA-DR抗体阻断，这表明T细胞反应对B-APC的抗原呈递具有特异性。HLA-DR也阻断了中枢神经系统抗原特异性CD8(+) T细胞增殖，这表明CD8(+)增殖部分依赖于CD4(+)辅助。
