Brimnes Marie Klinge, Hansen Bjarke Endel, Nielsen Leif Kofoed, Dziegiel Morten Hanefeld, Nielsen Claus Henrik
Institute for Inflammation Research, Department of Infectious Diseases and Rheumatology, section 7521, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.
Institute for Inflammation Research, Department of Infectious Diseases and Rheumatology, section 7521, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark; Immudex, Copenhagen, Denmark.
PLoS One. 2014 Nov 17;9(11):e113388. doi: 10.1371/journal.pone.0113388. eCollection 2014.
B cells may play both pathogenic and protective roles in T-cell mediated autoimmune diseases such as multiple sclerosis (MS). These functions relate to the ability of B cells to bind and present antigens. Under serum-free conditions we observed that 3-4% of circulating B cells from healthy donors were capable of binding the MS-associated self-antigen myelin basic protein (MBP) and of presenting the immunodominant peptide MBP85-99, as determined by staining with the mAb MK16 recognising the peptide presented by HLA-DR15-positive cells. In the presence of serum, however, the majority of B cells bound MBP in a complement-dependent manner, and almost half of the B cells became engaged in presentation of MBP85-99. Even though complement receptor 1 (CR1, CD35) and CR2 (CD21) both contributed to binding of MBP to B cells, only CR2 was important for the subsequent presentation of MBP85-99. A high proportion of MBP85-99 presenting B cells expressed CD27, and showed increased expression of CD86 compared to non-presenting B cells. MBP-pulsed B cells induced a low frequency of IL-10-producing CD4+ T cells in 3 out of 6 donors, indicating an immunoregulatory role of B cells presenting MBP-derived peptides. The mechanisms described here refute the general assumption that B-cell presentation of self-antigens requires uptake via specific B-cell receptors, and may be important for maintenance of tolerance as well as for driving T-cell responses in autoimmune diseases.
在诸如多发性硬化症（MS）等T细胞介导的自身免疫性疾病中，B细胞可能发挥致病和保护两种作用。这些功能与B细胞结合和呈递抗原的能力有关。在无血清条件下，我们观察到，通过用识别由HLA-DR15阳性细胞呈递的肽段的单克隆抗体MK16染色测定，来自健康供体的循环B细胞中有3%-4%能够结合MS相关自身抗原髓鞘碱性蛋白（MBP）并呈递免疫显性肽段MBP85-99。然而，在有血清存在的情况下，大多数B细胞以补体依赖的方式结合MBP，并且几乎一半的B细胞参与了MBP85-99的呈递。尽管补体受体1（CR1，CD35）和CR2（CD21）都有助于MBP与B细胞的结合，但只有CR2对随后MBP85-99的呈递很重要。高比例的呈递MBP85-99的B细胞表达CD27，并且与不呈递的B细胞相比，其CD86表达增加。用MBP脉冲处理的B细胞在6名供体中的3名中诱导产生了低频率的产生IL-10的CD4+T细胞，表明呈递MBP衍生肽段的B细胞具有免疫调节作用。这里描述的机制反驳了关于B细胞呈递自身抗原需要通过特定B细胞受体摄取的一般假设，并且对于维持耐受性以及在自身免疫性疾病中驱动T细胞反应可能很重要。
