Circulating regulatory B cell subsets in patients with neuromyelitis optica spectrum disorders

Han, Jinming; Sun, Li; Wang, Zhongkun; Fan, Xueli; Wang, Lifang; Song, Yangyang; Zhu, Jian

doi:10.1007/s10072-017-2932-7

Cited by 12 publications

(10 citation statements)

References 22 publications

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“…Currently, only a few studies have been conducted to explore the roles of TrB cells and TrB-associated molecules in NMOSDs. Specifically, fewer CD19 + CD24 hi CD38 hi TrB cells were found in those with NMOSDs than in those with MS [16,52]. The frequencies of CD19 + CD27 + memory B cells and mature B cells are not significantly different between those with NMOSDs and HC, whereas the percentage of CD19 + CD5 + CD1d hi Bregs decreased in NMOSDs cases [16,52].…”

Section: Trb Cells and Trb-associated Molecules In Neuromyelitis Optimentioning

confidence: 88%

“…We along with other investigators had previously shown that Bregs contribute to the maintenance of immune tolerance and modulation of immune responses [1,[51][52][53]. Currently, human Bregs have been noted at different stages of B cell development and consist of various B cell subsets, namely CD24 hi CD38 hi immature TrB cells [11], CD24 hi CD38 lo CD27 + memory B cells [54], and CD24 − CD38 + CD27 int IL-10-secreting plasmablasts [55].…”

Section: Transitional B Cells In Humansmentioning

confidence: 91%

“…Specifically, fewer CD19 + CD24 hi CD38 hi TrB cells were found in those with NMOSDs than in those with MS [16,52]. The frequencies of CD19 + CD27 + memory B cells and mature B cells are not significantly different between those with NMOSDs and HC, whereas the percentage of CD19 + CD5 + CD1d hi Bregs decreased in NMOSDs cases [16,52]. The proportion of TrB cells has been demonstrated to be lower in AQP4-positive group than in AQP4-negative group [16,52].…”

Section: Trb Cells and Trb-associated Molecules In Neuromyelitis Optimentioning

confidence: 99%

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Transitional B cells involved in autoimmunity and their impact on neuroimmunological diseases

et al. 2020

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Transitional B cells (TrB cells) represent a crucial link between immature B cells in the bone marrow and mature peripheral B cells. Although TrB cells represent one of the regulatory B cell subpopulations in healthy individuals, the frequency of CD24 hi CD38 hi TrB cells in circulation may be altered in individuals with autoimmune diseases, such as multiple sclerosis, neuromyelitisoptica spectrum disorders, systemic lupus erythematosus, Sjögren's syndrome, rheumatoid arthritis, systemic sclerosis, and juvenile dermatomyositis. Although TrB cells play regulatory roles under inflammatory conditions, consequences of their functional impairment vary across autoimmune diseases. Since the origin, development, and function of TrB cells, especially in humans, remain unclear and controversial, this review aimed to discuss the characteristics of TrB cells at steady state and explore their role in various immune diseases, including autoimmune rheumatic diseases and neuroimmunological diseases.

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Section: Trb Cells and Trb-associated Molecules In Neuromyelitis Optimentioning

confidence: 88%

Section: Transitional B Cells In Humansmentioning

confidence: 91%

Section: Trb Cells and Trb-associated Molecules In Neuromyelitis Optimentioning

confidence: 99%

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Transitional B cells involved in autoimmunity and their impact on neuroimmunological diseases

et al. 2020

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“…Breg cells are challenging to study, because of the lack of a good surface marker. Hence, in vitro stimulation is commonly used to assess Breg cell functionality and this is also the approach that we have used in this study. It is possible, that the in vitro stimulation protocol does not capture all the aspects of Breg cells influencing autoimmune pathophysiology and we can therefore not formally exclude that Breg cells function in ON is altered.…”

Section: Discussionmentioning

confidence: 99%

Frequency and immunophenotype of IL10‐producing regulatory B cells in optic neuritis

et al. 2018

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Mouse models of multiple sclerosis (MS) have shown the importance of interleukin-10 (IL-10) -producing regulatory B (Breg) cells in dampening disease activity and inhibiting disease initiation and progression. In MS and other autoimmune diseases decreased frequency and functionality of Breg cells correlate with disease activity and the percentage of IL-10-producing Breg cells decreases during relapse and normalizes in remission. Optic neuritis (ON) is a common first clinical manifestation of MS and IL-10-producing Breg cells may be crucial in the transition from ON to MS, we therefore investigate the frequency and function of Breg cells in ON as a clinical model of early demyelinating disease. B cells were purified from 27 patients with ON sampled close to symptom onset (median 23 days, range 7-41 days) and 13 healthy controls. The B cells were stimulated and cultured for 48 hr with CD40 ligand and CpG before measurement of intracellular IL-10 and the surface markers CD19, CD1d, CD5, CD24, CD38 and CD27 by flow cytometry. The frequency of B-cell subsets was analysed in peripheral blood and cerebral spinal fluid (CSF) of patients. Sixty-five per cent of the IL-10-producing Breg cells co-expressed CD24 and CD38, and only 14% were CD24 high CD27 + , suggesting that the naive B cells are the primary source of IL-10 in the B-cell culture, followed by memory cells in both healthy controls and patients. The frequency of naive CD19 + CD24 + CD38 + Breg cells was higher in patients with ON compared with controls. The ability of Breg cells to produce IL-10 was at normal levels in both ON patients with high risk and those with low risk of progression to MS. We found no correlation between Breg cell function and the presence of brain white matter lesions by magnetic resonance imaging or CSF oligoclonal bands indicative of ON patients carrying a higher risk of conversion to MS. The frequencies of IL-10-producing B cells did not correlate with the conversion to MS at 2-year follow up. Interleukin-10 was primarily produced by naive and memory B cells. The frequency of IL-10secreting B cells did not correlate with risk factors of MS. Breg cell function at clinical onset of ON is not a determining factor for conversion to MS.

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“…For example, a B cell subpopulation, exhibiting the CD19 int CD27 hi CD38 hi C180 – phenotype, was selectively increased in the peripheral blood of NMO patients and further expanded during NMOSD relapse, and AQP4-IgG was mainly produced by these cells in the blood [30]. A greater proportion of the circulating regulatory B cell subset, CD19 + CD24 hi CD27 + , was found in NMO patients than in healthy individuals, suggesting that this subset may participate in the pathogenesis of NMOSD [31]. However, whether levels of CSF sCD27 are elevated in NMO patients remains unknown.…”

Section: Discussionmentioning

confidence: 99%

Cerebrospinal Fluid Level of Soluble CD27 Is Associated with Disease Severity in Neuromyelitis Optica Spectrum Disorder

Liu¹,

Zhong²,

Liu³

et al. 2018

Neuroimmunomodulation

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Object: CD27 belongs to the tumor necrosis factor receptor family and is constitutively expressed on T cells. The concentration of cerebrospinal fluid (CSF) soluble (s)CD27 is elevated in patients with multiple sclerosis (MS). However, whether the level of CSF sCD27 is elevated in neuromyelitis optica spectrum disorder (NMOSD) remains unknown. The aim of this study was to measure the CSF concentration of sCD27 and to determine its relationship with NMOSD disease activity. Methods: CSF CXCL13 was measured by ELISA in neuromyelitis optica (NMO) (n = 31) and MS (n = 23) patients and in controls (CTLs) (n = 22). Results: The concentration of sCD27 was higher in the NMO group than in the MS (p = 0.082) and CTL (p = 0.002) groups, and there was a positive correlation with CSF IL-6 (p = 0.000) and a negative correlation with IL-10 (p = 0.073). In the NMO group, patients with higher sCD27 concentrations exhibited worse disease disability in their CSF (p = 0.006). Moreover, the sCD27 concentrations had a significantly positive correlation with the level of CSF total protein (p = 0.030). Furthermore, the patients positive for AQP4-IgG (n = 26) seemed to have higher levels of sCD27 in their CSF (p = 0.069) than those negative for AQP4-IgG (n = 5). Conclusions: We revealed that the level of CSF sCD27 was elevated in NMOSD and correlated with NMOSD disease activity.

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Circulating regulatory B cell subsets in patients with neuromyelitis optica spectrum disorders

Cited by 12 publications

References 22 publications

Transitional B cells involved in autoimmunity and their impact on neuroimmunological diseases

Transitional B cells involved in autoimmunity and their impact on neuroimmunological diseases

Frequency and immunophenotype of IL10‐producing regulatory B cells in optic neuritis

Cerebrospinal Fluid Level of Soluble CD27 Is Associated with Disease Severity in Neuromyelitis Optica Spectrum Disorder

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