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      Reassessing B cell contributions in multiple sclerosis

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      Nature Immunology
      Springer Nature America, Inc

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          Abstract

          <p class="first" id="d1730202e77">There is growing recognition that B cell contributions to normal immune responses extend well beyond their potential to become antibody-producing cells, including roles at the innate-adaptive interface and their potential to modulate the responses of other immune cells such as T cells and myeloid cells. These B cell functions can have both pathogenic and protective effects in the context of central nervous system (CNS) inflammation. Here, we review recent advances in the field of multiple sclerosis (MS), which has traditionally been viewed as primarily a T cell-mediated disease, and we consider antibody-dependent and, particularly, emerging antibody-independent functions of B cells that may be relevant in both the peripheral and CNS disease compartments. </p>

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          Most cited references156

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          Meningeal B-cell follicles in secondary progressive multiple sclerosis associate with early onset of disease and severe cortical pathology.

          Intrathecal antibody production is a hallmark of multiple sclerosis and humoral immunity is thought to play an important role in the inflammatory response and development of demyelinated lesions. The presence of lymphoid follicle-like structures in the cerebral meninges of some multiple sclerosis patients indicates that B-cell maturation can be sustained locally within the CNS and contribute to the establishment of a compartmentalized humoral immune response. In this study we examined the distribution of ectopic B-cell follicles in multiple sclerosis cases with primary and secondary progressive clinical courses to determine their association with clinical and neuropathological features. A detailed immunohistochemical and morphometric analysis was performed on post-mortem brain tissue samples from 29 secondary progressive (SP) and 7 primary progressive (PP) multiple sclerosis cases. B-cell follicles were detected in the meninges entering the cerebral sulci of 41.4% of the SPMS cases, but not in PPMS cases. The SPMS cases with follicles significantly differed from those without with respect to a younger age at multiple sclerosis onset, irreversible disability and death and more pronounced demyelination, microglia activation and loss of neurites in the cerebral cortex. Cortical demyelination in these SPMS cases was also more severe than in PPMS cases. Notably, all meningeal B-cell follicles were found adjacent to large subpial cortical lesions, suggesting that soluble factors diffusing from these structures have a pathogenic role. These data support an immunopathogenetic mechanism whereby B-cell follicles developing in the multiple sclerosis meninges exacerbate the detrimental effects of humoral immunity with a subsequent major impact on the integrity of the cortical structures.
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            Multiple Sclerosis Pathology

            Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS), which gives rise to focal lesions in the gray and white matter and to diffuse neurodegeneration in the entire brain. In this review, the spectrum of MS lesions and their relation to the inflammatory process is described. Pathology suggests that inflammation drives tissue injury at all stages of the disease. Focal inflammatory infiltrates in the meninges and the perivascular spaces appear to produce soluble factors, which induce demyelination or neurodegeneration either directly or indirectly through microglia activation. The nature of these soluble factors, which are responsible for demyelinating activity in sera and cerebrospinal fluid of the patients, is currently undefined. Demyelination and neurodegeneration is finally accomplished by oxidative injury and mitochondrial damage leading to a state of “virtual hypoxia.”
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              Is Open Access

              Human and nonhuman primate meninges harbor lymphatic vessels that can be visualized noninvasively by MRI

              Here, we report the existence of meningeal lymphatic vessels in human and nonhuman primates (common marmoset monkeys) and the feasibility of noninvasively imaging and mapping them in vivo with high-resolution, clinical MRI. On T2-FLAIR and T1-weighted black-blood imaging, lymphatic vessels enhance with gadobutrol, a gadolinium-based contrast agent with high propensity to extravasate across a permeable capillary endothelial barrier, but not with gadofosveset, a blood-pool contrast agent. The topography of these vessels, running alongside dural venous sinuses, recapitulates the meningeal lymphatic system of rodents. In primates, meningeal lymphatics display a typical panel of lymphatic endothelial markers by immunohistochemistry. This discovery holds promise for better understanding the normal physiology of lymphatic drainage from the central nervous system and potential aberrations in neurological diseases.
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                Author and article information

                Journal
                Nature Immunology
                Nat Immunol
                Springer Nature America, Inc
                1529-2908
                1529-2916
                July 2018
                June 20 2018
                July 2018
                : 19
                : 7
                : 696-707
                Article
                10.1038/s41590-018-0135-x
                29925992
                6e416cb2-729a-4966-803b-9028526b028f
                © 2018

                http://www.springer.com/tdm

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