• Chronic GVHD
• Natural history
• Phases
• Therapy discontinuation

• Humans
• Hematopoietic Stem Cell Transplantation/adverse effects
• Graft vs Host Disease
• Child
• Chronic Disease
• Adolescent

• I01 CX002721 CSRD VA
• IK2 CX001785 CSRD VA
• R01 HL169944 NHLBI NIH HHS
• R13 HL172559 NHLBI NIH HHS

• B cells
• host–pathogen interactions
• human
• parasitic–helminth
• proteomics

• Humans
• Adult
• Male
• Female
• Rural Population
• Child
• Memory B Cells/immunology
• Adolescent
• Middle Aged
• Indonesia
• Ghana
• Immunologic Memory/immunology
• Young Adult
• Child, Preschool
• B-Lymphocyte Subsets/immunology
• Tropical Climate
• Aged

• Dutch Lung Foundation
• vidi-91714352 Netherlands Science Council

• CD1c
• IL-10
• cAMP-response element-binding protein
• graft-versus-host disease
• mesenchymal stromal cells
• protein kinase A
• regulatory B cells

• Humans
• Graft vs Host Disease/immunology
• Graft vs Host Disease/etiology
• Animals
• Mice
• B-Lymphocytes, Regulatory/immunology
• B-Lymphocytes, Regulatory/metabolism
• Mesenchymal Stem Cells/metabolism
• Antigens, CD1/metabolism
• Interleukin-10/metabolism
• Signal Transduction
• Disease Models, Animal
• Cyclic AMP Response Element-Binding Protein/metabolism
• Tumor Necrosis Factor-alpha/metabolism
• Hematopoietic Stem Cell Transplantation/methods
• Hematopoietic Stem Cell Transplantation/adverse effects
• Glycoproteins

• Autoimmune diseases
• Breg makers
• Breg subsets
• Breg-based therapies
• Regulatory B cells

• Humans
• B-Lymphocytes, Regulatory/immunology
• B-Lymphocytes, Regulatory/metabolism
• Autoimmune Diseases/immunology
• Autoimmune Diseases/therapy
• Animals
• Signal Transduction
• Immune Tolerance

• Autoimmunity
• B cells
• Breg
• Cancer
• Cellular immunology
• Immune regulation
• Regulatory B cell

• B-Lymphocytes, Regulatory/immunology
• Humans
• Animals
• Autoimmunity/immunology
• Biomarkers
• B-Lymphocyte Subsets/immunology
• Neoplasms/immunology
• Homeostasis/immunology

• 176303 Versus Arthritis UK
• 185431 Lupus UK

• Liver transplantation
• NFAT5
• Regulatory B cells
• miR-29a-3p

• Humans
• MicroRNAs/metabolism
• MicroRNAs/genetics
• B-Lymphocytes, Regulatory/immunology
• B-Lymphocytes, Regulatory/metabolism
• Cell Differentiation
• Antigens, CD19/metabolism
• Antigens, CD19/genetics
• Liver Transplantation
• Male
• CD24 Antigen/metabolism
• CD24 Antigen/genetics
• Signal Transduction
• Graft Rejection/immunology
• Graft Rejection/genetics
• Female
• Transcription Factors/genetics
• Transcription Factors/metabolism
• Middle Aged
• Immune Tolerance
• Cells, Cultured
• Adult
• Phenotype
• Immunologic Memory

• B
• BAFF
• Bregs cells
• Cell abnormality
• Chronic graft
• Cyclosporin A
• Host disease
• Inflammatory factors
• Pro
• Rituximab
• Versus

• No.820MS137 Hainan Provincial Natural Science Foundation of China

• atypical B cell
• pan-cancer analysis
• single-cell RNA sequencing
• tumor-infiltrating B cell

• Humans
• Single-Cell Analysis
• Neoplasms/immunology
• Neoplasms/pathology
• B-Lymphocytes/immunology
• B-Lymphocytes/metabolism
• Phenotype
• Lymphocytes, Tumor-Infiltrating/immunology
• Lymphocytes, Tumor-Infiltrating/metabolism
• CD4-Positive T-Lymphocytes/immunology
• CD4-Positive T-Lymphocytes/metabolism
• B-Lymphocyte Subsets/immunology
• B-Lymphocyte Subsets/metabolism
• Immunoglobulin G/immunology
• Immunoglobulin G/metabolism
• Immunotherapy
• Prognosis

• Humans
• Hematopoietic Stem Cell Transplantation
• Graft vs Host Disease/etiology
• Hematologic Neoplasms/therapy
• Chronic Disease
• Healthcare Disparities
• Disease Management
• Bronchiolitis Obliterans Syndrome

• GraB cell
• Interleukin 10
• granzyme B
• immunosuppression
• regulatory B cell

• Humans
• Mice
• Animals
• Interleukin-10/metabolism
• B-Lymphocytes, Regulatory
• Prognosis
• Cytokines/metabolism
• Inflammation/metabolism
• Immunosuppressive Agents/therapeutic use

• graft-versus-host disease
• medical dermatology
• transplantation

• Humans
• Bronchiolitis Obliterans Syndrome
• Graft vs Host Disease/diagnosis
• Graft vs Host Disease/epidemiology
• Graft vs Host Disease/etiology
• Quality of Life
• Hematopoietic Stem Cell Transplantation/adverse effects
• Hematopoietic Stem Cell Transplantation/methods
• Skin/pathology
• Chronic Disease

• ZIA AR041227 Intramural NIH HHS

• GvHD pathogenesis
• cell-cell communication
• chronic graft-versus-host disease
• hematopoietic stem cell transplantation
• immune cell networks

• European Cooperation in Science and Technology
• LEO Fondet
• Narodowym Centrum Nauki

• B cell
• immunotherapy
• mechanism
• metabolism
• tumor metastasis

• Cellular biomarker
• Chronic graft-versus-host disease
• Hematopoietic stem cell transplantation

• B-lymphocytes
• T-lymphocytes
• immunomodulation
• immunotherapy
• melanoma

• T-Lymphocytes
• B-Lymphocytes
• Immunosuppressive Agents/pharmacology
• Sirolimus
• Immunotherapy

• P30 CA016672 NCI NIH HHS
• R01 CA231364 NCI NIH HHS
• P50 CA100632 NCI NIH HHS
• U01 CA247760 NCI NIH HHS
• R01 CA211044 NCI NIH HHS
• P01 CA148600 NCI NIH HHS
• Leukemia Specialized Program of Research Excellence (SPORE)
• Cancer Prevention and Research Institute of Texas
• National Cancer Institute
• Japan Society for the Promotion of Science (JSPS)

Sepsis still remains a major challenge in intensive care medicine with unacceptably high mortality among patients with septic shock. Due to current limitations of human CD19⁺CD24^hiCD38^hi Breg cells (Bregs) studies among sepsis, here, we tried to evaluate Bregs in severity and prognostic value in patients with sepsis.

Peripheral blood from 58 patients with sepsis and 22 healthy controls was analyzed using flow cytometry to evaluate the frequency and number of Bregs. All cases were divided into non-survived or survived group after 28 days followed up. Spearman's correlation analysis was performed on Bregs frequency and clinical indices. The area under the curve was acquired using the receiver operating characteristic analysis to assess the sensitivity and specificity of Bregs for outcome of sepsis. Survival curve analysis and binary logistic regression were applied to estimate the value of Bregs in prognosis among cases with sepsis.

Sepsis patients had decreased proportions and number of Bregs. Sepsis patients with low frequency of Bregs were associated with an increased risk of septic shock. Bregs frequency is inversely associated with lactate, SOFA, and APACHE II and positively correlated with Tregs frequency. Low levels of Bregs closely correlated with septic outcomes. Numbers of Bregs were prediction factors for poor prognosis.

Frequency and number of Bregs decreased, and Bregs deficiency revealed poor prognosis in patients with sepsis.

The online version contains supplementary material available at 10.1186/s12865-022-00528-x.

• sepsis
• flow cytometry
• b-lymphocytes
• interleukin-10
• regulatory b cells
• prognosis

• Antibodies, Neutralizing/metabolism
• B-Lymphocytes, Regulatory
• Biomarkers/metabolism
• Extracellular Matrix/metabolism
• Mesenchymal Stem Cells/metabolism
• Transforming Growth Factor beta/metabolism

• chronic allograft nephropathy
• inflammation
• lymphocytes
• transplantation

• Graft Rejection/prevention & control
• Histocompatibility
• Interferon-gamma/metabolism
• Kidney Transplantation/adverse effects
• Phenotype
• Prognosis

• MR/J006742/1 Medical Research Council
• MR/T025573/1 Medical Research Council

• allergen engineering
• allergen extract
• allergen‑specific immunotherapy
• component‑resolved diagnostics
• polyallergy

• Animals
• Antibodies, Viral
• B-Lymphocytes
• COVID-19
• Humans
• Immunologic Memory
• Mammals
• Memory B Cells
• SARS-CoV-2
• Vaccination
• Vaccines

• 75N93019C00051 NIAID NIH HHS
• P01 AI097092 NIAID NIH HHS
• P01 AI165077 NIAID NIH HHS
• U01 AI144616 NIAID NIH HHS

• Animals
• B-Lymphocytes, Regulatory
• CD8-Positive T-Lymphocytes
• Graft vs Host Disease/prevention & control
• Hematopoietic Stem Cell Transplantation/methods
• Mice
• Mice, Inbred C57BL

• Agence Nationale de la Recherche
• Conseil National de la Recherche Scientifique
• Institut National de la Santé et de la Recherche Médicale
• Fondation ARC pour la Recherche sur le Cancer

The presence of tumour-infiltrating immune cells was originally associated with the induction of anti-tumour responses and good a prognosis. A more refined characterization of the tumour microenvironment has challenged this original idea and evidence now exists pointing to a critical role for immune cells in the modulation of anti-tumour responses and the induction of a tolerant pro-tumour environment. The coordinated action of diverse immunosuppressive populations, both innate and adaptive, shapes a variety of pro-tumour responses leading to tumour progression and metastasis. Regulatory B cells have emerged as critical modulators and suppressors of anti-tumour responses. As reported in autoimmunity and infection studies, Bregs are a heterogeneous population with diverse phenotypes and different mechanisms of action. Here we review recent studies on Bregs from animal models and patients, covering a variety of types of cancer. We describe the heterogeneity of Bregs, the cellular interactions they make with other immune cells and the tumour itself, and their mechanism of suppression that enables tumour escape. We also discuss the potential therapeutic tools that may inhibit Bregs function and promote anti-tumour responses.

• IL-10
• Regulatory B cells
• Regulatory T cells
• tumour immunology

Systemic sclerosis (SSc) is a multisystem rheumatic disease characterized by vascular dysfunction, autoimmune abnormalities, and progressive organ fibrosis. A series of studies in SSc patients and fibrotic models suggest that immune cells, fibroblasts, and endothelial cells participate in inflammation and aberrant tissue repair. Furthermore, the growing number of studies on single-cell RNA sequencing (scRNA-seq) technology in SSc elaborate on the transcriptomics and heterogeneities of these cell subsets significantly. In this review, we summarize the current knowledge regarding immune cells and stromal cells in SSc patients and discuss their potential roles in SSc pathogenesis, focusing on recent advances in the new subtypes by scRNA-seq.

• cell therapy
• graft tolerance
• immunosuppressive therapy
• kidney transplantation
• regulatory B cells

• Chronic Disease
• Disease Management
• Graft vs Host Disease/etiology
• Graft vs Host Disease/pathology
• Graft vs Host Disease/prevention & control
• Graft vs Host Disease/therapy
• Humans
• Immunomodulating Agents/therapeutic use
• Male
• Middle Aged
• Protein Kinase Inhibitors/therapeutic use

• Breg exhaustion
• CD24(hi)CD38(hi) regulatory B cells
• IL-10
• Stable chronic obstructive pulmonary disease

• ADP-ribosyl Cyclase 1/blood
• ADP-ribosyl Cyclase 1/immunology
• Aged
• B-Lymphocytes, Regulatory/immunology
• Biomarkers/blood
• CD24 Antigen/blood
• CD24 Antigen/immunology
• Female
• Humans
• Interleukin-10/blood
• Interleukin-10/immunology
• Leukocytes, Mononuclear/immunology
• Lymphocyte Count/methods
• Male
• Pulmonary Disease, Chronic Obstructive/blood
• Pulmonary Disease, Chronic Obstructive/immunology

• Breg cells
• Th17 cells
• autoimmune uveitis
• mesenchymal stem cells

• B regulatory cells
• GC B cells
• T follicular helper cells
• T follicular regulatory cells
• combination immunotherapy
• germinal center
• immune checkpoint
• lymphoma

• PID2020-112994RB-I00/AEI/10.13039/501100011033 Agencia Estatal de Investigación
• SAF2017-82309-R/MINECO/AEI/FEDER, EU Ministerio de Economía, Industria y Competitividad, Gobierno de España
• Gobierno de Navarra 34E/2020 Departamento de Educación, Gobierno de Navarra
• RYC-2014-16399/MEC Ministerio de Economía y Competitividad

• Animals
• Aspergillosis/microbiology
• Aspergillosis/pathology
• B-Lymphocytes/pathology
• B-Lymphocytes/physiology
• Capillaries/pathology
• Cell Adhesion
• Chemokine CXCL13/metabolism
• Integrin alpha5/metabolism
• Intravital Microscopy
• Lipoxins/metabolism
• Lung/blood supply
• Lung/diagnostic imaging
• Lung/pathology
• Mice, Mutant Strains
• Neutrophils/pathology
• Pneumonia/diagnostic imaging
• Pneumonia/pathology
• Receptors, CXCR5/metabolism
• Single-Cell Analysis
• Mice

• RS-342013 CIHR
• Canada Foundation for Innovation
• John R. Evans Leaders Fund
• Alberta Enterprise and Advanced Education Research Capacity Program
• Canadian Institutes of Health Research
• Calgary Firefighters Burn Treatment Society
• Alberta Children’s Hospital Research Institute

For the establishment of a successful infection, i.e., long-term parasitism and a complete life cycle, parasites use various diverse mechanisms and factors, which they may be inherently bestowed with, or may acquire from the natural vector biting the host at the infection prelude, or may take over from the infecting host, to outmaneuver, evade, overcome, and/or suppress the host immunity, both innately and adaptively. This narrative review summarizes the up-to-date strategies exploited by a number of representative human parasites (protozoa and helminths) to counteract the target host immune defense. The revisited information should be useful for designing diagnostics and therapeutics as well as vaccines against the respective parasitic infections.

• alternatively activated macrophages
• antigenic disguise
• antigenic mimicry
• immune checkpoints
• immunological privilege sites
• insect vectors
• parasite immune evasion
• regulatory immune cells

Allogeneic stem cell transplantation survivors are at a relevant risk of developing chronic GvHD (cGvHD), which importantly affects quality of life and increases morbidity and mortality. Early identification of patients at risk of cGvHD-related morbidity could represent a relevant tool to tailor preventive strategies. The aim of this study was to evaluate the prognostic power of immune reconstitution (IR) at cGvHD onset through an IR-based score.

We analyzed data from 411 adult patients consecutively transplanted between January 2011 and December 2016 at our Institution: 151 patients developed cGvHD (median follow-up 4 years). A first set of 111 consecutive patients with cGvHD entered the test cohort while an additional consecutive 40 patients represented the validation cohort. A Cox multivariate model for OS (overall survival) in patients with cGvHD of any severity allowed the identification of six variables independently predicting OS and TRM (transplant-related mortality). A formula for a prognostic risk index using the β coefficients derived from the model was designed. Each patient was assigned a score defining three groups of risk (low, intermediate, and high).

Our multivariate model defined the variables independently predicting OS at cGvHD onset: CD4+ >233 cells/mm³, NK <115 cells/mm³, IgA <0.43g/L, IgM <0.45g/L, Karnofsky PS <80%, platelets <100x10³/mm³. Low-risk patients were defined as having a score ≤3.09, intermediate-risk patients >3.09 and ≤6.9, and high-risk patients >6.9. By ROC analysis, we identified a cut-off of 6.310 for both TRM and overall mortality.

In the training cohort, the 6-year OS and TRM from cGvHD occurrence were 85% (95% CI, 70-92) and 13% (95% CI, 5-25) for low-risk, 64% (95% CI, 44-89) and 30% (95% CI, 15-47) for intermediate-risk, 26% (95% CI, 10-47), and 42% (95% CI, 19-63) for high-risk patients (OS p<0.0001; TRM p = 0.015).

The validation cohort confirmed the model with a 6-year OS and TRM of 83% (95% CI, 48-96) and 8% (95% CI, 1-32) for low-risk, 78% (95% CI, 37-94) and 11% (95% CI, 1-41) for intermediate-risk, 37% (95% CI, 17-58), and 63% (95% CI, 36-81) for high-risk patients (OS p = 0.0075; TRM p = 0.0009).

IR score at diagnosis of cGvHD predicts GvHD severity and overall survival. IR score may contribute to the risk stratification of patients. If confirmed in a larger and multicenter-based study, IR score could be adopted to identify patients at high risk and modulate cGvHD treatments accordingly in the context of clinical trial.

• biomarker
• chronic GvHD
• immune reconstitution
• overall survival
• prognostic score

• Chronic graft-versus-host disease
• Cord blood transplantation
• Hematopoietic stem cell transplantation
• Immune reconstruction
• Peripheral blood stem cell transplantation

• Cord Blood Stem Cell Transplantation
• Graft vs Host Disease
• Hematopoietic Stem Cell Transplantation
• Humans
• Immune Reconstitution
• Peripheral Blood Stem Cell Transplantation
• Siblings

• 31870897 National Natural Science Foundation of China
• WK9110000001 The Fundamental Research Funds for the Central Universities
• 1804h08020245 Key Research and Development Projects in Anhui Province

• AITD
• IL-10
• Regulatory B cells

The Identification of B cell subsets with regulatory functions might open the way to new therapeutic strategies in the field of transplantation, which aim to reduce the dose of immunosuppressive drugs and prolong the graft survival. CD25 was proposed as a marker of a B-cell subset with an immunosuppressive action termed Bregs. The effect of CD19 + CD25 + Bregs on graft function in renal transplant recipients has not yet been elucidated. We investigated a potential impact of CD19 + CD25 + Bregs on renal graft function as well as a possible interaction of CD19 + CD25 + Bregs with peripheral Tregs in healthy controls, end-stage kidney disease patients (ESKD), and renal transplant recipients. Moreover, we aimed to investigate the association of CD19 + CD25 + Bregs with serum IL-10, TGF-ß1, and IFN-γ in the same study groups.

Thirty-one healthy controls, ninety renal transplant recipients, and eighteen ESKD patients were enrolled. We evaluated the CD19 + CD25 + Bregs and Treg absolute counts. Next, we investigated CD19 + CD25 + Bregs as predictors of good graft function in multiple regression and ROC analyses. Finally, we evaluated the association between CD19 + CD25+ Bregs and serum IL-10, TGF-ß, and IFN-γ.

ESKD patients and renal transplant recipients showed lower counts of CD19 + CD25+ Bregs compared to healthy controls (p < 0.001). Higher CD19 + CD25+ Breg counts were independently associated with a better GFR in renal transplant recipients (unstandardized B coefficient = 9, p = 0.02). In these patients, higher CD19 + CD25+ Bregs were independently associated with higher Treg counts (unstandardized B = 2.8, p = 0.004). In ROC analysis, cut-offs for CD19 + CD25 + Breg counts and serum TGF-ß1 of 0.12 cell/μl and 19,635.4 pg/ml, respectively, were shown to provide a good sensitivity and specificity in identifying GFR ≥ 30 ml/min (AUC = 0.67, sensitivity 77%, specificity 43%; AUC = 0.65, sensitivity 81%, specificity 50%, respectively). Finally, a significant positive association between CD19 + CD25+ Bregs and TGF-ß1 was shown in renal transplant recipients (r = 0.255, p = 0.015).

Our findings indicate that higher counts of CD19 + CD25+ Bregs are independently associated with better renal function and higher absolute Treg counts in renal transplant recipients.

The online version contains supplementary material available at 10.1186/s12882-021-02374-2.

• Bregs
• GFR
• Renal transplantation
• Tregs

• CD1d
• IL-10
• IL-35
• PD-L1
• TGF-β
• TIM-1
• granzyme B
• regulatory B cells

• graft-versus-host disease
• pathophysiology
• prevention
• regulation
• therapy
• tolerance

• Animals
• Graft vs Host Disease/etiology
• Graft vs Host Disease/therapy
• Hematologic Neoplasms
• Hematopoietic Stem Cell Transplantation/adverse effects
• Humans
• Transplantation Conditioning
• Transplantation, Homologous

• R01 HL133823 NHLBI NIH HHS
• R01 HL095791 NHLBI NIH HHS
• R01 FD004099 FDA HHS
• P01 CA065493 NCI NIH HHS
• R01 HL118979 NHLBI NIH HHS
• U19 AI051731 NIAID NIH HHS
• R01 HL147324 NHLBI NIH HHS
• R37 AI034495 NIAID NIH HHS
• R01 HL155114 NHLBI NIH HHS
• R01 HL056067 NHLBI NIH HHS
• U01 CA244291 NCI NIH HHS
• P01 AI056299 NIAID NIH HHS
• R01 HL148164 NHLBI NIH HHS
• P01 CA142106 NCI NIH HHS

• Airway inflammation
• Allergic asthma
• Human immunology
• IgE+ B cells
• Inhaled allergen challenge
• Regulatory B cells
• Sputum

• Immune reconstitution
• haploidentical hematopoietic stem cell transplantation
• post-transplant cyclophosphamide

• B-Lymphocytes/immunology
• B-Lymphocytes/metabolism
• Biomarkers
• Combined Modality Therapy
• Cyclophosphamide/administration & dosage
• HLA Antigens/genetics
• HLA Antigens/immunology
• Hematopoietic Stem Cell Transplantation/adverse effects
• Hematopoietic Stem Cell Transplantation/methods
• Humans
• Immune Reconstitution
• Immunophenotyping
• Leukocyte Count
• Leukocytes/immunology
• Leukocytes/metabolism
• Lymphocyte Depletion
• Postoperative Care
• T-Lymphocyte Subsets
• T-Lymphocytes/cytology
• T-Lymphocytes/immunology
• T-Lymphocytes/metabolism
• Time Factors
• Transplantation, Haploidentical
• Treatment Outcome