B Lymphocytes in Multiple Sclerosis: Bregs and BTLA/CD272 Expressing-CD19+ Lymphocytes Modulate Disease Severity

Piancone, Federica; Saresella, Marina; Marventano, Ivana; Rosa, Francesca La; Zoppis, Martina; Agostini, Simone; Longhi, Renato; Caputo, Domenico; Mendozzi, Laura; Rovaris, Marco; Clerici, Mario

doi:10.1038/srep29699

Cited by 36 publications

(19 citation statements)

References 61 publications

(73 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Recently, the role of memory B cells as a target for DMTs has been highlighted [ 14 , 117 ] and Baker et al [ 14 ] have proposed that memory B cell depletion may represent a common, unifying mechanism of action for DMTs [ 14 ]. Interestingly, it has been suggested that the secretion of functionally diverse cytokines by B cells may play a role in determining MS disease phenotypes [ 118 ]. In addition, it has been shown that a subgroup of patients with MS display brain-reactive B cell responses that may be associated with clinical relapse [ 33 ]; the clinical relevance of this observation is not yet clear.…”

Section: Summary and Future Perspectivesmentioning

confidence: 99%

Impact of Glatiramer Acetate on B Cell-Mediated Pathogenesis of Multiple Sclerosis

et al. 2018

View full text Add to dashboard Cite

Growing evidence indicates that B cells play a key role in the pathogenesis of multiple sclerosis (MS). B cells occupy distinct central nervous system (CNS) compartments in MS, including the cerebrospinal fluid and white matter lesions. Also, it is now known that, in addition to entering the CNS, B cells can circulate into the periphery via a functional lymphatic system. Data suggest that the role of B cells in MS mainly involves their in situ activation in demyelinating lesions, leading to altered pro- and anti-inflammatory cytokine secretion, and a highly effective antigen-presenting cell function, resulting in activation of memory or naïve T cells. Clinically, B cell-depleting agents show significant efficacy in MS. In addition, many disease-modifying therapies (DMTs) traditionally understood to target T cells are now known to influence B cell number and function. One of the earliest DMTs to be developed, glatiramer acetate (GA), has been shown to reduce the total frequency of B cells, plasmablasts, and memory B cells. It also appears to promote a shift toward reduced inflammation by increasing anti-inflammatory cytokine release and/or reducing pro-inflammatory cytokine release by B cells. In the authors’ opinion, this may be mediated by cross-reactivity of B cell receptors for GA with antigen (possibly myelin basic protein) expressed in the MS lesion. More research is required to further characterize the role of B cells and their bidirectional trafficking in the pathogenesis of MS. This may uncover novel targets for MS treatments and facilitate the development of B cell biomarkers of drug response.

show abstract

Section: Summary and Future Perspectivesmentioning

confidence: 99%

Impact of Glatiramer Acetate on B Cell-Mediated Pathogenesis of Multiple Sclerosis

et al. 2018

View full text Add to dashboard Cite

show abstract

“…There are ample reports in the literature examining how Bregs function and develop [ 59 ], but this review will focus on the role of regulatory B-cells in MS. To begin with, several groups have demonstrated that B-cells taken from MS patients produce less IL-10 compared to B-cells taken from healthy controls. These MS B-cells also produce less IL-10 upon stimulation with Cpg [ 60 ] or MOG peptide [ 61 ].…”

Section: B-cells In Multiple Sclerosis (Ms)mentioning

confidence: 99%

Emerging Role of Follicular T Helper Cells in Multiple Sclerosis and Experimental Autoimmune Encephalomyelitis

Quinn

Axtell

2018

IJMS

View full text Add to dashboard Cite

Multiple sclerosis (MS) is an autoimmune disorder where both T cells and B cells are implicated in pathology. However, it remains unclear how these two distinct populations cooperate to drive disease. There is ample evidence from studies in both MS patients and mouse models that Th17, B cells, and follicular T helper (TFH) cells contribute to disease. This review article describes the literature that identifies mechanisms by which Th17, TFH, and B cells cooperatively drive disease activity in MS and experimental autoimmune encephalomyelitis (EAE). The curation of this literature has identified that central nervous system (CNS) infiltrating TFH cells act with TH17 cell to contribute to an inflammatory B cell response in neuroinflammation. This demonstrates that TFH cells and their products are promising targets for therapies in MS.

show abstract

“…The underlying mechanisms for MS are considered autoimmune due to the pivotal role of the body's own immune system in disease progression [28]. The immunopathological process in MS is mediated by T and B cells and activated macrophages that are involved in the demyelination of axons, thereby inducing severe tissue damage and neuronal dysfunction [29,30].…”

Section: Multiple Sclerosismentioning

confidence: 99%

Inflammation at the blood-brain barrier: The role of liver X receptors

Wit

Vanmol

Kamermans

et al. 2017

Neurobiology of Disease

View full text Add to dashboard Cite

The blood-brain barrier (BBB) is indispensable for the maintenance of brain homeostasis and proper neuronal functioning. Dysfunction of the BBB significantly contributes to the pathogenesis of neuroinflammatory and neurodegenerative diseases like stroke, multiple sclerosis (MS), and Alzheimer's disease (AD). The neuroinflammatory environment that characterizes these disorders propagates chronic impaired function of the BBB, processes that will be discussed in this review. Limiting dysfunction of the BBB may be an attractive target for treatment of neurological disorders. To date, no current treatments are directly targeting the function of the BBB. In this review, we will specifically discuss the potential protective role of nuclear liver X receptors (LXRs) as a promising therapeutic target to reverse or prevent BBB impairment in neurological diseases.

show abstract

B Lymphocytes in Multiple Sclerosis: Bregs and BTLA/CD272 Expressing-CD19+ Lymphocytes Modulate Disease Severity

Cited by 36 publications

References 61 publications

Impact of Glatiramer Acetate on B Cell-Mediated Pathogenesis of Multiple Sclerosis

Impact of Glatiramer Acetate on B Cell-Mediated Pathogenesis of Multiple Sclerosis

Emerging Role of Follicular T Helper Cells in Multiple Sclerosis and Experimental Autoimmune Encephalomyelitis

Inflammation at the blood-brain barrier: The role of liver X receptors

Contact Info

Product

Resources

About