The Role of B Cells in Primary Progressive Multiple Sclerosis.
The Role of B Cells in Primary Progressive Multiple Sclerosis.
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DOI：
10.3389/fneur.2021.680581
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发表时间：
2021
影响因子：
3.4
通讯作者：
Wu GF
中科院分区：
文献类型：
--
作者：
Holloman JP;Axtell RC;Monson NL;Wu GF
ocrelizumab通过cd20靶向耗竭减少原发性进行性多发性硬化症（PPMS）中已证实的残疾积累，这表明B细胞是PPMS发病机制中的致病因子。这篇综述探讨了B细胞促进PPMS疾病进展的可能机制，特别是探索细胞因子产生、抗原呈递和抗体合成。B细胞可能通过细胞因子的产生促进PPMS的疾病进展，特别是GM-CSF和IL-6，它们可以驱动naïve t细胞分化为促炎的Th1/Th17细胞。B细胞产生的细胞因子LT-α可能诱导滤泡树突状细胞产生CXCL13，并间接导致T细胞和B细胞浸润到中枢神经系统。相反，B细胞产生IL-10可能诱导抗炎作用，可能在减少PPMS的神经炎症中发挥作用。因此，IL-10的减少可能导致疾病恶化。B细胞也能够有效的抗原呈递，并可能通过同源相互作用诱导促炎t细胞分化。B细胞也可能通过抗体合成促进疾病活动，尽管ocrelizumab对PPMS的益处不太可能通过抗体减少发生。最后，多种B细胞亚群可能在多发性硬化症中发挥促炎或抗炎作用。
The success of ocrelizumab in reducing confirmed disability accumulation in primary progressive multiple sclerosis (PPMS) via CD20-targeted depletion implicates B cells as causal agents in the pathogenesis of PPMS. This review explores the possible mechanisms by which B cells contribute to disease progression in PPMS, specifically exploring cytokine production, antigen presentation, and antibody synthesis. B cells may contribute to disease progression in PPMS through cytokine production, specifically GM-CSF and IL-6, which can drive naïve T-cell differentiation into pro-inflammatory Th1/Th17 cells. B cell production of the cytokine LT-α may induce follicular dendritic cell production of CXCL13 and lead indirectly to T and B cell infiltration into the CNS. In contrast, production of IL-10 by B cells likely induces an anti-inflammatory effect that may play a role in reducing neuroinflammation in PPMS. Therefore, reduced production of IL-10 may contribute to disease worsening. B cells are also capable of potent antigen presentation and may induce pro-inflammatory T-cell differentiation via cognate interactions. B cells may also contribute to disease activity via antibody synthesis, although it's unlikely the benefit of ocrelizumab in PPMS occurs via antibody decrement. Finally, various B cell subsets likely promulgate pro- or anti-inflammatory effects in MS.
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影响因子：
11.1
作者：
Baker D;Marta M;Pryce G;Giovannoni G;Schmierer K
通讯作者：
Schmierer K
影响因子：
7.5
作者：
Arruda, Lucas C. M.;Malmegrim, Kelen C. R.;Oliveira, Maria Carolina
通讯作者：
Oliveira, Maria Carolina
DOI：
10.1073/pnas.0402455101
发表时间：
2004-07-27
影响因子：
11.1
作者：
Corcione, A;Casazza, S;Pistoia, V
通讯作者：
Pistoia, V
DOI：
10.1084/jem.20111675
发表时间：
2012-05-07
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
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通讯作者：
Gray D
影响因子：
9.9
作者：
Eikelenboom, MJ;Petzold, A;Uitdehaag, BMJ
通讯作者：
Uitdehaag, BMJ