OBJECTIVE: To explore the role of follicular helper T cell (Tfh)/ follicular regulatory T cell (Tfr) imbalance in B-cell lymphoma (BCL). METHODS: Sixteen BCL patients who were admitted to the Department of Hematology of The First People's Hospital of Yichang and 20 healthy people from December 2019 to November 2020 were enrolled and respectively divided into observation group and control group. The levels of Tfh and Tfr in peripheral blood were detected by flow cytometry. The changes of Tfh, Tfr, and Tfh/Tfr ratio were compared and the relationship between Tfh/Tfr ratio and efficacy, prognosis was analyzed. RESULTS: Compared with the healthy controls, Tfh and Tfh/Tfr ratio in peripheral blood of the BCL patients increased (P<0.05, P<0.01), while levels of Tfr was decreased (P<0.01). After chemotherapy, Tfh and Tfh/Tfr ratio in peripheral blood of the BCL patients decreased significantly than before chemotherapy (P<0.01), but Tfr was no significant difference. Multivariate analysis showed that Tfh and Tfh/Tfr ratio were positively correlated with international prognostic index (IPI) score and Ann Arbor stage (r=0.626, 0.564, 0.573, 0.608, respectively), while Tfr negatively (r=－0.504, －0.542, respectively). According to the average value of Tfh/Tfr ratio at initial diagnosis, BCL patients were divided into Tfh/Tfr high ratio group and low ratio group. It was found that the complete remission (CR) rate, overall response rate (ORR), and survival time in the high ratio group were significantly lower than the low ratio group (P<0.01). CONCLUSION There is an imbalance of Tfh/Tfr ratio in peripheral blood of the BCL patients, and those with a high Tfh/Tfr ratio have lower CR, ORR and shorter survival time.
Flow Cytometry ; Humans ; Lymphoma, B-Cell ; T Follicular Helper Cells ; T-Lymphocytes, Helper-Inducer ; T-Lymphocytes, Regulatory

Since primary Sjögren's syndrome (pSS) is an autoummune disease of B cell hyperactivity and pathologic autoantibody response, follicular helper T (Tfh) cells and follicular regulatory T (Tfr) cells are suggested to be key players in pSS. We examined subsets of Tfh and Tfr cells from the blood in pSS patients, and whether these subsets represent disease activity, glandular inflammation, or autoantibody responses in pSS. Circulating Tfh and Tfr cells, along with their specific subsets, were identified from the peripheral blood of 18 pSS patients and 14 age- and sex-matched healthy controls (HCs) using flow cytometry analysis. Blood Tfr and Tfh cell ratios were increased in pSS patients compared with HCs. The CCR7(lo)PD-1(hi) subset of circulating Tfh cells was increased in pSS patients with high degree of focal lymphocytic sialadenitis; whereas circulating Tfh cells did not differ between pSS patients and HCs. The frequency of CCR7(lo)PD-1(hi) Tfh cells was significantly correlated with disease activity scores and differentiated B cells. PD-1 expression on blood Tfh and Tfr cells showed positive correlations with IL-21 in pSS. Increasing trend of blood Tfr cells was observed in pSS patients, and blood Tfr cells (particularly Th1 and Th17 subsets) represented hypergammaglobulinemia in pSS. In summary, circulating CCR7(lo)PD-1(hi) Tfh cells indicated disease activity and glandular inflammation in pSS. Circulating Tfr cells, shifted toward Th1 and Th17 subsets, indicated ongoing IgG production in pSS. Subsets of circulating Tfh or Tfr cells could be biomarkers for disease monitoring and patient stratification in pSS.
Autoantibodies ; B-Lymphocytes ; Biomarkers ; Flow Cytometry ; Humans ; Hypergammaglobulinemia ; Immunoglobulin G ; Inflammation ; Sialadenitis ; T-Lymphocyte Subsets ; T-Lymphocytes ; T-Lymphocytes, Helper-Inducer ; T-Lymphocytes, Regulatory

B cells play a role in graft rejection via several mechanisms. Specifically, B cells produce high-affinity antibodies to alloantigens including allogeneic major histocompatibility complex (MHC) with the help of follicular helper T cells. B cells also function as antigen-presenting cells for alloreactive T cells, resulting in the activation of alloreactive T cells. Conversely, the frequency of regulatory B cells increases under inflammatory conditions and suppresses the rejection process. Here, the differential roles of the major B cell subpopulations (B-1, follicular B, marginal zone B, and regulatory B cells) involved in transplantation rejection are discussed together with their interaction with T cells.
Antibodies ; Antibody Diversity ; Antigen-Presenting Cells ; B-Lymphocytes* ; B-Lymphocytes, Regulatory ; Graft Rejection* ; Isoantigens ; Major Histocompatibility Complex ; T-Lymphocytes ; T-Lymphocytes, Helper-Inducer

Foxp3 is a transcript factor for regulatory T cell development. Interestingly, Foxp3-expressing cells were identified in B cells, especially in CD19(+)CD5(+) B cells, while those were not examined in CD19(+)CD5(-) B cells. Foxp3-expressing CD5(+) B cells in this study were identified in human PBMCs and were found to consist of 8.5+/-3.5% of CD19(+)CD5(+) B cells. CD19(+)CD5(+)Foxp3(+) B cells showed spontaneous apoptosis. Rare CD19(+)CD5(+) Foxp3(+) regulatory B cell (Breg) population was unveiled in human peripheral blood mononuclear cells and suggested as possible regulatory B cells (Breg) as regulatory T cells (Treg). The immunologic and the clinical relevant of Breg needs to be further investigated.
Apoptosis ; B-Lymphocytes ; B-Lymphocytes, Regulatory ; Humans ; T-Lymphocytes, Regulatory

Understanding germinal center reactions is crucial not only for the design of effective vaccines against infectious agents and malignant cells but also for the development of therapeutic intervention for the treatment of antibody-mediated immune disorders. Recent advances in this field have revealed specialized subsets of T cells necessary for the control of B cell responses in the follicle. These cells include follicular regulatory T cells and Qa-1-restricted cluster of differentiation (CD)8+ regulatory T cells. In this review, we discuss the current knowledge related to the role of regulatory T cells in the B cell follicle.
Germinal Center ; Immune System Diseases ; T-Lymphocytes ; T-Lymphocytes, Helper-Inducer ; T-Lymphocytes, Regulatory* ; Vaccines

Follicular helper T cells (Tfh) play a significant role in providing T cell help to B cells during the germinal center reaction, where somatic hypermutation, affinity maturation, isotype class switching, and the differentiation of memory B cells and long-lived plasma cells occur. Antigen-specific T cells with IL-6 and IL-21 upregulate CXCR5, which is required for the migration of T cells into B cell follicles, where these T cells mature into Tfh. The surface markers including PD-1, ICOS, and CD40L play a significant role in providing T cell help to B cells. The upregulation of transcription factor Bcl-6 induces the expression of CXCR5, which is an important factor for Tfh differentiation, by inhibiting the expression of other lineage-specific transcription factors such as T-bet, GATA3, and RORgammat. Surprisingly, recent evidence suggests that CD4 T cells already committed to Th1, Th2, and Th17 cells obtain flexibility in their differentiation programs by downregulating T-bet, GATA3, and RORgammat, upregulating Bcl-6 and thus convert into Tfh. Limiting the numbers of Tfh within germinal centers is important in the regulation of the autoantibody production that is central to autoimmune diseases. Recently, it was revealed that the germinal center reaction and the size of the Tfh population are also regulated by thymus-derived follicular regulatory T cells (Tfr) expressing CXCR5 and Foxp3. Dysregulation of Tfh appears to be a pathogenic cause of autoimmune disease suggesting that tight regulation of Tfh and germinal center reaction by Tfr is essential for maintaining immune tolerance. Therefore, the balance between Tfh and Tfr appears to be a critical peripheral tolerance mechanism that can inhibit autoimmune disorders.
Autoimmune Diseases ; Autoimmunity ; B-Lymphocytes ; CD40 Ligand ; Germinal Center ; Immune Tolerance ; Immunoglobulin Class Switching ; Interleukin-6 ; Interleukins ; Memory ; Nuclear Receptor Subfamily 1, Group F, Member 3 ; Peripheral Tolerance ; Plasma Cells ; Pliability ; T-Lymphocytes ; T-Lymphocytes, Helper-Inducer ; T-Lymphocytes, Regulatory ; Th17 Cells ; Transcription Factors ; Up-Regulation

Follicular helper T (TFH) cells are recently highlighted as their crucial role for humoral immunity to infection as well as their abnormal control to induce autoimmune disease. During an infection, naive T cells are differentiating into TFH cells which mediate memory B cells and long-lived plasma cells in germinal center (GC). TFH cells are characterized by their expression of master regulator, Bcl-6, and chemokine receptor, CXCR5, which are essential for the migration of T cells into the B cell follicle. Within the follicle, crosstalk occurs between B cells and TFH cells, leading to class switch recombination and affinity maturation. Various signaling molecules, including cytokines, surface molecules, and transcription factors are involved in TFH cell differentiation. IL-6 and IL-21 cytokine-mediated STAT signaling pathways, including STAT1 and STAT3, are crucial for inducing Bcl-6 expression and TFH cell differentiation. TFH cells express important surface molecules such as ICOS, PD-1, IL-21, BTLA, SAP and CD40L for mediating the interaction between T and B cells. Recently, two types of microRNA (miRNA) were found to be involved in the regulation of TFH cells. The miR-17-92 cluster induces Bcl-6 and TFH cell differentiation, whereas miR-10a negatively regulates Bcl-6 expression in T cells. In addition, follicular regulatory T (TFR) cells are studied as thymus-derived CXCR5+PD-1+Foxp3+ Treg cells that play a significant role in limiting the GC response. Regulation of TFH cell differentiation and the GC reaction via miRNA and TFR cells could be important regulatory mechanisms for maintaining immune tolerance and preventing autoimmune diseases such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Here, we review recent studies on the various factors that affect TFH cell differentiation, and the role of TFH cells in autoimmune diseases.
Arthritis, Rheumatoid ; Autoimmune Diseases ; Autoimmunity* ; B-Lymphocytes ; CD40 Ligand ; Cell Differentiation ; Cytokines ; Germinal Center ; Immune Tolerance ; Immunity, Humoral ; Interleukin-6 ; Lupus Erythematosus, Systemic ; Memory ; MicroRNAs ; Negotiating ; Plasma Cells ; Recombination, Genetic ; T-Lymphocytes ; T-Lymphocytes, Helper-Inducer* ; T-Lymphocytes, Regulatory ; Transcription Factors

OBJECTIVE: To investigate the role of regulatory B cells (Breg) in pathogenesis of immune thrombocytopenia(ITP) and its clinical significance. METHODS: A total of 40 ITP patients and 20 normal controls were enrolled in this study. The content of Breg, Th1, Th2, Th17 and Treg cells were detected by flow cytometry (FCM). The expression level of IL-10,TGF-β, CD40 and CD40L was detected by AimPlex Flow High Throughput Screening Technology. RESULTS: The of Breg cells in ITP patients was significantly lower than that in normal controls (P<0.05)，the expression levels of IL-10,TGF-β and CD40L in ITP patients were also significantly lower than those in normal controls (P<0.05). The contents of Th1 cells in ITP patients were significantly higher than that in normal controls (P<0.05), whereas the contents of Th2, Th17 and Treg cells in ITP patients were significantly lower than those in normal controls (P<0.05). CONCLUSION The Breg cells may play an important role in the pathogenesis of ITP.
B-Lymphocytes, Regulatory ; Humans ; T-Lymphocytes, Regulatory ; Th17 Cells ; Thrombocytopenia

To investigate the effects of chemerin on helper T cells 9 (Th9)/regulatory T cells (Treg) in patients with psoriasis and the potential molecular mechanisms.
 Methods: Twenty-five patients with psoriasis and twenty healthy volunteers were selected for this study. CD4+ T cells were isolated from peripheral blood of samples by magnetic bead separation. The levels of chemerin and its receptor chemR23 were detected by real-time RT-PCR and ELISA. CD4+ T cells isolated from the healthy volunteers were treated with different concentrations of chemerin (50, 100, 150, 200 ng/mL), then cell viability was detected by MTT assay. The expression of inflammatory molecules and Th9/Treg were detected by ELISA and flow cytometry, respectively.
 Results: The expressions of chemerin and chemR23 in peripheral blood from patients with psoriasis were higher than those in healthy control (both P<0.05). The Th9/Treg was higher in patients with psoriasis than that in healthy control (P<0.05). After treating CD4+ T cells with 150 ng/mL of chemerin, the levels of IL-6, IL-9 and IL-17 were increased significantly (all P<0.05). Additionally, Th9/Treg was increased (P<0.05) and the cell balance was disrupt. However, the effects of chemerin on CD4+ T cells were reversed by silencing of chemR23 (all P<0.05).
 Conclusion: Chemerin may regulate the immune balance for Th9/Treg in CD4+ T cells from patients of psoriasis.
Chemokines ; Flow Cytometry ; Humans ; Intercellular Signaling Peptides and Proteins ; Psoriasis ; T-Lymphocytes, Helper-Inducer ; T-Lymphocytes, Regulatory

The notion that obesity-induced inflammation mediates the development of insulin resistance in animal models and humans has been gaining strong support. It has also been shown that immune cells in local tissues, in particular in visceral adipose tissue, play a major role in the regulation of obesity-induced inflammation. Specifically, obesity increases the numbers and activation of proinflammatory immune cells, including M1 macrophages, neutrophils, Th1 CD4 T cells, and CD8 T cells, while simultaneously suppressing anti-inflammatory cells such as M2 macrophages, CD4 regulatory T cells, regulatory B cells, and eosinophils. Recently, however, new cell types have been shown to participate in the development of obesity-induced inflammation and insulin resistance. Some of these cell types also appear to regulate obesity. These cells are natural killer (NK) cells and innate lymphoid cells (ILCs), which are closely related, and invariant natural killer T (iNKT) cells. It should be noted that, although iNKT cells resemble NK cells in name, they are actually a completely different cell type in terms of their development and functions in immunity and metabolism. In this review, we will focus on the roles that these relatively new players in the metabolism field play in obesity-induced insulin resistance and the regulation of obesity.
B-Lymphocytes, Regulatory ; Diabetes Mellitus, Type 2 ; Eosinophils ; Humans ; Inflammation* ; Insulin Resistance* ; Insulin* ; Intra-Abdominal Fat ; Killer Cells, Natural* ; Lymphocytes ; Macrophages ; Metabolism ; Models, Animal ; Natural Killer T-Cells* ; Neutrophils ; Obesity ; T-Lymphocytes ; T-Lymphocytes, Regulatory