Understanding regulatory B cells in autoimmune diseases: the case of multiple sclerosis

Cuc, Bui Thi; Pohar, Jelka; Fillatreau, Simon

doi:10.1016/j.coi.2019.07.007

Cited by 21 publications

(12 citation statements)

References 64 publications

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“…Transitional B cells are enriched in IL-10 producing cells. Their relative abundance contributes to a more regulatory immune state (7,30). However, our ex vivo and in vitro data did not underpin a negative or positive direct effect of BAFF or BAFF-R shift on IL-10 production.…”

Section: Discussioncontrasting

confidence: 54%

“…BAFF is increasingly recognized as a key factor in B cell development, survival, immunoglobulin production and T cell stimulation ( 6 ). Transitional B cells are enriched for regulatory cells producing interleukin-10 (IL-10) ( 7 ) while memory B cells are more likely to have a pro-inflammatory function driving relapsing disease ( 8 ). A spontaneous BAFF increase has been observed in other autoimmune diseases and can correlate with disease progression ( 9 , 10 ).…”

Section: Introductionmentioning

confidence: 99%

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Treatment-Induced BAFF Expression and B Cell Biology in Multiple Sclerosis

et al. 2021

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Although fingolimod and interferon-β are two mechanistically different multiple sclerosis (MS) treatments, they both induce B cell activating factor (BAFF) and shift the B cell pool towards a regulatory phenotype. However, whether there is a shared mechanism between both treatments in how they influence the B cell compartment remains elusive. In this study, we collected a cross-sectional study population of 112 MS patients (41 untreated, 42 interferon-β, 29 fingolimod) and determined B cell subsets, cell-surface and RNA expression of BAFF-receptor (BAFF-R) and transmembrane activator and cyclophilin ligand interactor (TACI) as well as plasma and/or RNA levels of BAFF, BAFF splice forms and interleukin-10 (IL-10) and -35 (IL-35). We added an in vitro B cell culture with four stimulus conditions (Medium, CpG, BAFF and CpG+BAFF) for untreated and interferon-β treated patients including measurement of intracellular IL-10 levels. Our flow experiments showed that interferon-β and fingolimod induced BAFF protein and mRNA expression (P ≤ 3.15 x 10-4) without disproportional change in the antagonizing splice form. Protein BAFF correlated with an increase in transitional B cells (P = 5.70 x 10-6), decrease in switched B cells (P = 3.29 x 10-4), and reduction in B cell-surface BAFF-R expression (P = 2.70 x 10-10), both on TACI-positive and -negative cells. TACI and BAFF-R RNA levels remained unaltered. RNA, plasma and in vitro experiments demonstrated that BAFF was not associated with increased IL-10 and IL-35 levels. In conclusion, treatment-induced BAFF correlates with a shift towards transitional B cells which are enriched for cells with an immunoregulatory function. However, BAFF does not directly influence the expression of the immunoregulatory cytokines IL-10 and IL-35. Furthermore, the post-translational mechanism of BAFF-induced BAFF-R cell surface loss was TACI-independent. These observations put the failure of pharmaceutical anti-BAFF strategies in perspective and provide insights for targeted B cell therapies.

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Section: Discussioncontrasting

confidence: 54%

Section: Introductionmentioning

confidence: 99%

Treatment-Induced BAFF Expression and B Cell Biology in Multiple Sclerosis

et al. 2021

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“…However, little research about the interaction of 5-HT and some novel immune cells has been reported. Recently, regulatory B cells have attracted widespread attention for their function in autoimmune diseases such as IBD and MS (124,125). Besides, innate lymphoid cells have been considered as regulators of immunity, inflammation, and tissue homeostasis (126).…”

Section: Discussionmentioning

confidence: 99%

Serotonin: A Potent Immune Cell Modulator in Autoimmune Diseases

et al. 2020

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Serotonin, also known as 5-hydroxytryptamine (5-HT) is a signaling mediator that regulates emotion, behavior, and cognition. Previous studies have focused more on the roles of 5-HT in the central nervous system (CNS). However, 5-HT also shares a strong relationship with the pathological cases of tumor, inflammation, and pathogen infection. 5-HT participates in tumor cell migration, metastatic dissemination, and angiogenesis. In addition, 5-HT affects immune regulation via different 5-HT receptors (5-HTRs) expressed immune cells, including both innate and adaptive immune system. Recently, drugs targeting at 5-HT signaling were tested to be beneficial in mouse models and clinical trials of multiple sclerosis (MS) and inflammatory bowel disease (IBD). Thus, it is reasonable to assume that 5-HT participates in the pathogenesis of autoimmune diseases. However, the underlying mechanism by 5-HT modulates the development of autoimmune diseases has not been fully understood. Based on our previous studies and pertinent literature, we provide circumstantial evidence for an essential role of 5-HT, especially the regulation of 5-HT on immune cells in the pathogenesis of autoimmune diseases, which may provide a new point cut for the treatment of autoimmune diseases.

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“…Overall, B cells represent a crucial population with particular properties to present autoantigen to T cells in MS patients, both within CNS and in the peripheral immune compartments. B cells are also an important source of many proinflammatory cytokines that are likely to promote autoregressive and encephalitogenic reactions [34,35]. B cells from patients with MS show increased expression of the immunostimulatory nuclear factor κB after activation via the CD40 molecule [36].…”

Section: Role Of B Cells In Autoimmune Demyelination and B Cell Targementioning

confidence: 99%

B cell targeting therapies in MS patients during the SARS-CoV-2 pandemic — when immunosuppression meets infection?

Mycko

2020

Neurol Neurochir Pol.

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Introduction. Research into the mechanisms of autoimmune demyelination have highlighted B cells in this process. Therapies targeting this population were a recent addition to the multiple sclerosis (MS) drugs portfolio. The SARS-CoV-2 pandemic and the risk of severe COVID-19 have challenged the safety of B cell depletion in MS patients. State of the art. Selective depletion of B cells by monoclonal antibodies as monotherapy in MS has been shown to profoundly suppress disease activity among relapsing-remitting MS patients. Furthermore ocrelizumab, a humanised anti-CD20 monoclonal antibody, was the first licensed therapy in primary progressive MS. Based on the concept of the role of B cells in MS, many therapeutic approaches are emerging as novel ways to treat autoimmune demyelination. However, during the SARS-CoV-2 pandemic, a conservative approach toward limiting immune suppression in MS patients has been proposed. Clinical implications. Emerging evidence does not support the notion of increased susceptibility among MS patients to the SARS-CoV-2 infection, or any predisposition toward greater severity of COVID-19. This also does not appear to be the case for MS patients undergoing B cell depletion therapies. Thus, any decision to withhold immune suppression in MS patients during the SARS-CoV-2 pandemic is probably incorrect. MS therapeutic decision-making should focus on the danger of poorly controlled autoimmune demyelination rather than perceived risks from COVID-19. Future directions. The current pandemic highlights the need to develop more selective and safer methods of immunomodulation in MS. B cells represent several functionally different populations. Further research into the different role of these cells during autoimmune demyelination should yield better, safer strategies to control the encephalitogenic process.

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Understanding regulatory B cells in autoimmune diseases: the case of multiple sclerosis

Cited by 21 publications

References 64 publications

Treatment-Induced BAFF Expression and B Cell Biology in Multiple Sclerosis

Treatment-Induced BAFF Expression and B Cell Biology in Multiple Sclerosis

Serotonin: A Potent Immune Cell Modulator in Autoimmune Diseases

B cell targeting therapies in MS patients during the SARS-CoV-2 pandemic — when immunosuppression meets infection?

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