In gray matter pathology of multiple sclerosis, neurodegeneration associates with a high degree of meningeal inflammatory activity. Importantly, ectopic lymphoid follicles (eLFs) were identified at the inflamed meninges of patients with progressive multiple sclerosis. Besides T lymphocytes, they comprise B cells and might elicit germinal center (GC)-like reactions. GC reactions are controlled by FOXP3⁺ T-follicular regulatory cells (T_FR), but it is unknown if they participate in autoantibody production in eLFs. Receiving human post-mortem material, gathered from autopsies of progressive multiple sclerosis patients, indeed, distinct inflammatory infiltrates enriched with B cells could be detected in perivascular areas and deep sulci. CD35⁺ cells, parafollicular CD138⁺ plasma cells, and abundant expression of the homing receptor for GCs, CXCR5, on lymphocytes defined some of them as eLFs. However, they resembled GCs only in varying extent, as T cells did not express PD-1, only few cells were positive for the key transcriptional regulator BCL-6 and ongoing proliferation, whereas a substantial number of T cells expressed high NFATc1 like GC-follicular T cells. Then again, predominant cytoplasmic NFATc1 and an enrichment with CD3⁺CD27⁺ memory and CD4⁺CD69⁺ tissue-resident cells implied a chronic state, very much in line with PD-1 and BCL-6 downregulation. Intriguingly, FOXP3⁺ cells were almost absent in the whole brain sections and CD3⁺FOXP3⁺ T_FRs were never found in the lymphoid aggregates. This also points to less controlled humoral immune responses in those lymphoid aggregates possibly enabling the occurrence of CNS-specific autoantibodies in multiple sclerosis patients.

在多发性硬化症的灰质病理中，神经退行性变与高度脑膜炎性活动有关。重要的是，在进行性多发性硬化症患者的发炎的脑膜上发现了异位淋巴滤泡（eLF）。除T淋巴细胞外，它们还包含B细胞，并可能引起生发中心（GC）样反应。GC反应受FOXP3 ⁺ T卵泡调节细胞（T _FR）的控制，但尚不清楚它们是否参与eLFs自身抗体的产生。从进行性多发性硬化症患者尸检中收集的人体验尸材料的确，可以在血管周围区域和深沟中检测到富含B细胞的炎性浸润。CD35 ⁺细胞，滤泡旁CD138 ⁺浆细胞以及GC上归巢受体CXCR5在淋巴细胞上的大量表达将其中一些定义为eLF。但是，它们仅在不同程度上类似于GC，因为T细胞不表达PD-1，只有少数细胞对关键的转录调节因子BCL-6呈阳性并正在进行增殖，而大量T细胞像GC-一样表达高NFATc1。滤泡性T细胞。然后，主要的细胞质NFATc1以及CD3 ⁺ CD27 ⁺记忆和CD4 ⁺ CD69 ⁺组织驻留细胞的富集暗示了一种慢性状态，这与PD-1和BCL-6的下调非常一致。有趣的是，FOXP3 ⁺细胞在整个脑切片几乎不存在和CD3 ⁺ FOXP3 ⁺ Ť _FR S IN的淋巴聚集物从来没有发现。这也表明那些淋巴样聚集体中的体液免疫反应受到的控制较少，可能使多发性硬化症患者出现中枢神经系统特异性自身抗体。