Altered frequencies of memory B cells in new-onset systemic lupus erythematosus patients

Zhu, Li; Yin, Zijing; Ju, Bomiao; Zhang, Jing; Wang, Yanhua; Lv, Xiaoyi; Hao, Zhiming

doi:10.1007/s10067-017-3877-1

Cited by 35 publications

(31 citation statements)

References 26 publications

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“…Our study demonstrated that LN patients had significantly higher DN B cells than non-LN patients, suggesting that DN B cells are involved in the renal damage associated with SLE. This result is consistent with previous studies that showed DN B cells expanded in patients with LN (16,21). In addition, the levels of DN B cells were positively correlated to 24 h-UPE, suggesting that DN B cells may be involved in the severity of renal damage in LN patients.…”

Section: Discussionsupporting

confidence: 92%

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Double Negative B Cell Is Associated With Renal Impairment in Systemic Lupus Erythematosus and Acts as a Marker for Nephritis Remission

et al. 2020

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Objective: Recent studies on double negative B cells (DN B cells) suggested that they have potential pathogenic roles in systemic lupus erythematosus (SLE). This study aimed to determine the circulating DN B cells in SLE patients and analyzed the clinical significance of this cell subset. Methods: Fifty-seven SLE patients and fifty healthy controls (HCs) were recruited in this study. Among the 57 SLE patients, 25 had lupus nephritis (LN). All patients were followed up for 24 weeks. Peripheral B cell subsets were analyzed by flow cytometry. Results: DN B cells were significantly elevated in the SLE patients, especially in the patients with LN (p < 0.01). DN B showed a positive correlation with 24-h urine protein excretion (24 h-UPE) levels (r = 0.444, p = 0.034) in LN patients, and inversely correlated with evaluated glomerular filtration rate (eGFR) (r = −0.351, p = 0.011). DN B cells had a positive correlation with plasma cells (r = 0.484, p < 0.001) and memory B cells (r = 0.703, p < 0.001). After treatment, decreased DN B cells were associated with LN alleviation (p = 0.002). In the follow-up, the remission rate of LN patients with decreased DN B cells was significantly higher than LN patients with increased DN B cells (83.33 vs. 25.00%, p = 0.030) at week 24. Conclusions: This study suggests that the peripheral DN B cells are positively correlated with the severity of renal damage in LN patients and may potentially be used as a prognostic marker in LN.

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Section: Discussionsupporting

confidence: 92%

“…It has been proposed that DN B cells are involved in the pathogenesis of SLE. DN B cells were reported to be correlated with anti-dsDNA and anti-RNP/Sm autoantibodies (19)(20)(21). However, the detailed clinical relevance of DN B cells in SLE remains unclear.…”

Section: Introductionmentioning

confidence: 99%

Double Negative B Cell Is Associated With Renal Impairment in Systemic Lupus Erythematosus and Acts as a Marker for Nephritis Remission

et al. 2020

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“…integrin in a subset of SLE patients, implying reduced potential for TS B cells to access GALT in these cases. Data presented here implicates GALT as an important site for MZB differentiation and MZB depletion has been reported in SLE (Rodriguez-Bayona et al, 2010;Zhu et al, 2018). Hence, we sought to determine whether our proposed MZB differentiation pathway was defective in SLE.…”

Section: Marginal Zone B Cell Differentiation Is Defective In Patientmentioning

confidence: 88%

“…DN2 cells may be derived from activated naïve B cells (aNAV), driven by TLR7 engagement, resulting in the generation of self-reactive antibody producing plasma cells (Jenks et al, 2018;Tipton et al, 2015). Interestingly, a recent study of a cohort of newly diagnosed patients with SLE demonstrated that MZB may be reduced in frequency (Zhu et al, 2018…”

Section: T Tsmentioning

confidence: 99%

Human marginal zone B cell development from early T2 progenitors

Tull¹,

Pitcher²,

Guesdon³

et al. 2020

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B cells emerge from the bone marrow as transitional (TS) B cells that differentiate through T1, T2 and T3 stages to become naïve B cells. We have identified a bifurcation of human B cell maturation from the T1 stage forming IgMhi and IgMlo developmental trajectories. IgMhi T2 cells have higher expression of α4β7 integrin and lower expression of IL4 receptor (IL4R) compared to the IgMlo branch and are selectively recruited into gut-associated lymphoid tissue. IgMhi T2 cells also share transcriptomic features with marginal zone B cells (MZB). Lineage progression from T1 cells to MZB via an IgMhi trajectory is identified by pseudotime analysis of scRNA-sequencing data. Reduced frequency of IgMhi gut homing T2 cells is observed in severe SLE and is associated with reduction of MZB and their putative IgMhi precursors. The collapse of the gut-associated MZB maturational axis in severe SLE affirms its existence and importance for maintaining health.

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“…The B cell repertoire has crucial pathogenic roles in LN which include synthesis of autoantibodies, presentation of autoantigens, and secretion of pro-inflammatory and anti-inflammatory mediators that regulate the immune response (29)(30)(31)(32)(33)(34)(35)(36). Accumulating evidence suggests that SLE is associated with perturbations in B lymphocyte subpopulations, epitomized by an expansion of class-switched memory B cells relative to naïve cells in active lupus patients compared to patients during disease quiescence (10,37,38). Changes in B cell subtypes pertaining to LN relapse, however, remain to be characterized.…”

Section: Discussionmentioning

confidence: 99%

B Cell Subsets and Cellular Signatures and Disease Relapse in Lupus Nephritis

et al. 2020

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Introduction: Renal relapses adversely affect the long-term outcomes of patients with lupus nephritis (LN), but the pathogenic mechanisms remain elusive. B cell signatures of miR-148a, BACH1, BACH2, and PAX5 expression are relevant to the regulation of B lymphocyte homeostasis. It is unknown whether B cell signature is related to the relapse of LN. Methods: We compared B lymphocyte subsets and cellular signatures during disease quiescence between LN patients with multiple relapses (MR, ≥3 LN relapses within 36 months) and those with no relapse (NR). Also, circulating B lymphocytes were isolated from treatment-naïve patients with active LN and treated with antagomir-148a in vitro to investigate the relationship between miR-148a, BACH1, BACH2, and PAX5. Results: MR patients (n = 19), when compared with NR (n = 14), showed significantly lower percentage of circulating naïve B cells and higher memory B cell-to-naïve B cell ratio. MR patients also showed higher miR-148a levels in sera and B cells, and lower BACH1, BACH2, and PAX5 expression in naïve and memory B cells. Antagomir-148a upregulated BACH1, BACH2, and PAX5 expression, and reduced B cell proliferation upon stimulation, in naïve and memory B cells isolated from treatment-naïve active LN patients. Conclusion: Altered B cell subsets and cellular signatures of miR-148a, BACH1, BACH2, and PAX5 may be associated with distinct patient phenotypes related to the risk of LN relapse.

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Altered frequencies of memory B cells in new-onset systemic lupus erythematosus patients

Cited by 35 publications

References 26 publications

Double Negative B Cell Is Associated With Renal Impairment in Systemic Lupus Erythematosus and Acts as a Marker for Nephritis Remission

Double Negative B Cell Is Associated With Renal Impairment in Systemic Lupus Erythematosus and Acts as a Marker for Nephritis Remission

Human marginal zone B cell development from early T2 progenitors

B Cell Subsets and Cellular Signatures and Disease Relapse in Lupus Nephritis

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