Regulatory B-cells expand in peripheral blood of pregnant women having normal pregnancies but are very low in women suffering from spontaneous abortions

IntroductionCheckpoint-Inhibition (CPI) with PD-1- and PD-L1-inhibitors is a well-established therapy for advanced stage melanoma patients. CPI mainly acts via T-lymphocytes. However, recent literature suggests also a role for B cells modulating its efficacy and tolerability of CPI.Case ReportWe report a 48-year-old female patient with metastatic melanoma affecting brain, lung, skin and lymph nodes. A preexisting granulomatosis with polyangiitis was treated with rituximab over five years prior to the diagnosis of melanoma, resulting in a complete depletion of B cells both in peripheral blood as well as the tumor tissue. In the absence of the mutation of the proto-oncogene b-raf, treatment with the PD-1 inhibitor nivolumab was initiated. This therapy was well tolerated and resulted in a deep partial response, which is ongoing for 14+ months. Flow cytometric analysis of peripheral blood mononuclear cells revealed 15% IL-10 producing and 14% CD24 and CD38 double positive regulatory B cells.ConclusionThe exceptional clinical response to nivolumab monotherapy in our patient with depleted B cells sheds a new light on the relevance of B cells in the modulation of immune responses to melanoma. Obviously, B cells were not required for the efficacy of CPI in our patient. Moreover, the depletion of regulatory B cells may have improved efficacy of CPI.

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Frequency of CD19+CD24hiCD38hi regulatory B cells is decreased in peripheral blood and synovial fluid of patients with juvenile idiopathic arthritis: a preliminary study

Pediatric Rheumatology ◽

10.1186/s12969-018-0262-9 ◽

2018 ◽

Vol 16 (1) ◽

Cited By ~ 6

Author(s):

Qianzi Zhao ◽

Lawrence K. Jung

Keyword(s):

Juvenile Idiopathic Arthritis ◽

B Cells ◽

Synovial Fluid ◽

Peripheral Blood ◽

Regulatory B Cells ◽

Preliminary Study

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An Immunological Perspective: What Happened to Pregnant Women After Recovering From COVID-19?

Frontiers in Immunology ◽

10.3389/fimmu.2021.631044 ◽

2021 ◽

Vol 12 ◽

Author(s):

Sijia Zhao ◽

Ting Xie ◽

Li Shen ◽

Hong Liu ◽

Liling Wang ◽

...

Keyword(s):

B Cells ◽

Cord Blood ◽

Pregnant Women ◽

Umbilical Cord ◽

Umbilical Cord Blood ◽

Peripheral Blood ◽

Immune Cell ◽

Immune Cell Subsets ◽

Significant Difference ◽

The Impact

The coronavirus disease 2019 (COVID-19) pandemic has been raging around the world since January 2020. Pregnancy places the women in a unique immune scenario which may allow severe COVID‐19 disease. In this regard, the potential unknown effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on mothers and fetuses have attracted considerable attention. There is no clear consistent evidence of the changes in the immune status of pregnant women after recovery from COVID-19. In this study, we use multiparameter flow cytometry and Luminex assay to determine the immune cell subsets and cytokines, respectively, in the peripheral blood and umbilical cord blood from pregnant women recovering from COVID-19 about 3 months (n=5). Our results showed decreased percentages of Tc2, Tfh17, memory B cells, virus-specific NK cells, and increased percentages of naive B cells in the peripheral blood. Serum levels of IL-1ra and MCP-1 showed a decreased tendency in late recovery stage (LRS) patients. Meanwhile, there was no significant difference in immune cell subsets in the umbilical cord blood. The placentas from LRS patients showed increased CD68+ macrophages infiltration and mild hypoxic features. The inflammatory damage of the placenta may be related to the antiviral response. Since the receptors, ACE2 and TMPRSS2, utilized by SARS-CoV-2 are not co-expressed in the placenta, so it is extremely rare for SARS-CoV-2 to cause infection through this route and the impact on the fetus is negligible.

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330 Characterization of multiple B cell subsets in peripheral blood of psoriasis patients identifies a correlation of regulatory B cells and disease severity

Journal of Investigative Dermatology ◽

10.1016/j.jid.2016.06.350 ◽

2016 ◽

Vol 136 (9) ◽

pp. S217

Author(s):

M. Küpper ◽

J. Thomas ◽

N. Garzorz-Stark ◽

L. Krause ◽

N.S. Müller ◽

...

Keyword(s):

B Cells ◽

B Cell ◽

Disease Severity ◽

Peripheral Blood ◽

Regulatory B Cells ◽

B Cell Subsets

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Defective Regulatory B Cells Are Associated With Thyroid-Associated Ophthalmopathy

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2018-01812 ◽

2019 ◽

Vol 104 (9) ◽

pp. 4067-4077 ◽

Cited By ~ 1

Author(s):

Guo Chen ◽

Yungang Ding ◽

Qian Li ◽

Yanbing Li ◽

Xiaofeng Wen ◽

...

Keyword(s):

T Cells ◽

B Cells ◽

Peripheral Blood ◽

Mononuclear Cells ◽

Healthy Controls ◽

Regulatory B Cells ◽

Peripheral Blood Mononuclear ◽

Thyroid Associated Ophthalmopathy ◽

Ifn Γ

Abstract Purpose To investigate the change in IL-10–producing regulatory B cells (Breg), which suppress peripheral immune responses, in patients with thyroid-associated ophthalmopathy (TAO). Methods Peripheral blood mononuclear cells (PBMCs) were isolated from healthy controls (n = 54), patients with Graves disease (n = 26), and patients with TAO (N=125), and stimulated with CpG/CD40L. The frequency of IL-10–producing Bregs and the expression of IL-10 in response to TSH stimulation were measured by flow cytometry. CD4+ T cells were cultured with Breg-depleted PBMCs to elucidate the function of Bregs in patients with TAO. The potential immunoregulatory mechanism was also investigated by Western blot and chromatin immunoprecipitation assays. Results Patients with active TAO had higher baseline levels of Bregs in their peripheral blood than both healthy controls and inactive patients. TSH promoted Bregs. Bregs from patients with TAO were defective in suppressing the activation of interferon (IFN)-γ+ and IL-17+ T cells in vitro. Conclusions Regulatory B cells in patients with TAO are functionally defective, suggesting that the defective Bregs might be responsible for the pathogenesis of TAO.

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Circulating CD19+CD24hiCD38hi regulatory B cells as biomarkers of response to methotrexate in early rheumatoid arthritis

Rheumatology ◽

10.1093/rheumatology/keaa186 ◽

2020 ◽

Vol 59 (10) ◽

pp. 3081-3091

Author(s):

Paula Fortea-Gordo ◽

Alejandro Villalba ◽

Laura Nuño ◽

María José Santos-Bórnez ◽

Diana Peiteado ◽

...

Keyword(s):

T Cell ◽

B Cells ◽

B Cell ◽

Clinical Response ◽

Peripheral Blood ◽

Mononuclear Cells ◽

Regulatory B Cells ◽

Cell Frequency ◽

Peripheral Blood Mononuclear ◽

Inflammatory Conditions

Abstract Objective The protagonism of regulatory B cells seems to vary along the course of the disease in murine models of inflammatory conditions. Decreased numbers of circulating regulatory CD19+CD24hiCD38hi transitional (cTr) B cells have been described in patients with long-standing RA, thus our objective was to examine the frequency and evolution of cTr B cells in the peripheral blood of early RA (ERA) patients. Methods Freshly isolated peripheral blood mononuclear cells from 48 steroid- and DMARD-naïve ERA patients with a disease duration of <24 weeks and 48 healthy controls (HCs) were examined by flow cytometry. Co-cultures of isolated memory B cells were established with autologous T cells in the absence or presence of Tr B cells. Results As compared with HCs, ERA patients demonstrated an increased frequency of cTr B cells. cTr B cells of ERA patients and HCs displayed an anti-inflammatory cytokine profile and were able to downregulate T cell IFN-γ and IL-21 production, together with ACPA secretion in autologous B/T cell co-cultures. Basal frequencies of cTr B cells above the median value observed in HCs were associated with a good EULAR response to MTX at 12 months [relative risk 2.91 (95% CI 1.37, 6.47)]. A significant reduction of cTr B cells was observed 12 months after initiating MTX, when the cTr B cell frequency was no longer elevated but decreased, and this was independent of the degree of clinical response or the intake of prednisone. Conclusion An increased frequency of regulatory cTr B cells is apparent in untreated ERA and the baseline cTr B cell frequency is associated with the clinical response to MTX at 12 months.

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