scholarly journals Cognate T and B cell interaction and association of Follicular helper T cells with B cell responses inVibrio choleraeO1 infected Bangladeshi adults

2018 ◽  
Author(s):  
Rasheduzzaman Rashu ◽  
Taufiqur Rahman Bhuiyan ◽  
Mohammad Rubel Hoq ◽  
Lazina Hossain ◽  
Anik Paul ◽  
...  
Keyword(s):  
T Cells ◽  
B Cell ◽  
Vibrio Cholerae ◽  
Natural Infection ◽  
Cell Maturation ◽  
Cell Responses ◽  
Tfh Cells ◽  
Follicular Helper ◽  
B Cell Maturation ◽  
B Cell Responses

AbstractVibrio choleraeO1 can cause life threatening diarrheal disease if left untreated. A long lasting immune response, producing 3-5 years of protection from subsequent, symptomatic disease following natural infection, is mediated by B cell mediated humoral immunity. T cells can play critical roles in inducing such immunity. However, the mechanism of T cell dependent B cell maturation and whether a key sub-population of T cells are involved is not well established in cholera. We hypothesized that a specific population of T cells, follicular helper T (Tfh) cells, are involved in B cell maturation following cholera; we used flow cytometry, culture and colorimetric assays to address this question. We found thatV. choleraeinfection induces significant increase in circulating Tfh cells expressing B cell maturation associated protein CD40L early in disease. The increased Tfh cells expressing CD40L recognize cholera toxin most prominently, with lessened responses to two antigens tested,V. choleraemembrane preparation (MP) andVibrio choleraecytolysin (VCC). We further showed that early induction of Tfh cells and CD40L was associated with later memory B cell responses to same antigens. Lastly, we demonstratedin vitrothat Tfh cells isolated after cholera can stimulate class switching of cocultured, isolated B cells from patients with cholera, leading to production of the more durable IgG antibody isotype. These studies were conducted on circulating Tfh cells; future studies will be directed at examining role of Tfh cells during cholera directly in the gut mucosa of biopsied samples, at the single cell level if feasible.

scholarly journals Cognate T and B cell interaction and association of follicular helper T cells with B cell responses in Vibrio cholerae O1 infected Bangladeshi adults

2019 ◽  
Vol 21 (3-4) ◽  
pp. 176-183 ◽  
Author(s):  
Rasheduzzaman Rashu ◽  
Taufiqur Rahman Bhuiyan ◽  
Mohammad Rubel Hoq ◽  
Lazina Hossain ◽  
Anik Paul ◽  
...  
Keyword(s):  
T Cells ◽  
B Cell ◽  
Vibrio Cholerae ◽  
Cell Interaction ◽  
Helper T Cells ◽  
Follicular Helper T Cells ◽  
Cell Responses ◽  
Follicular Helper ◽  
Vibrio Cholerae O1 ◽  
B Cell Responses

scholarly journals Regulation of Intrinsic and Bystander T Follicular Helper Cell Differentiation and Autoimmunity by Tsc1

2021 ◽  
Vol 12 ◽  
Author(s):  
Shimeng Zhang ◽  
Lei Li ◽  
Danli Xie ◽  
Srija Reddy ◽  
John W. Sleasman ◽  
...  
Keyword(s):  
T Cells ◽  
Cell Differentiation ◽  
Immune Responses ◽  
B Cell ◽  
Regulatory Cells ◽  
Wild Type ◽  
Autoantibody Production ◽  
Cell Responses ◽  
Tfh Cells ◽  
Follicular Helper

T Follicular helper (Tfh) cells promote germinal center (GC) B cell responses to develop effective humoral immunity against pathogens. However, dysregulated Tfh cells can also trigger autoantibody production and the development of autoimmune diseases. We report here that Tsc1, a regulator for mTOR signaling, plays differential roles in Tfh cell/GC B cell responses in the steady state and in immune responses to antigen immunization. In the steady state, Tsc1 in T cells intrinsically suppresses spontaneous GC-Tfh cell differentiation and subsequent GC-B cell formation and autoantibody production. In immune responses to antigen immunization, Tsc1 in T cells is required for efficient GC-Tfh cell expansion, GC-B cell induction, and antigen-specific antibody responses, at least in part via promoting GC-Tfh cell mitochondrial integrity and survival. Interestingly, in mixed bone marrow chimeric mice reconstituted with both wild-type and T cell-specific Tsc1-deficient bone marrow cells, Tsc1 deficiency leads to enhanced GC-Tfh cell differentiation of wild-type CD4 T cells and increased accumulation of wild-type T regulatory cells and T follicular regulatory cells. Such bystander GC-Tfh cell differentiation suggests a potential mechanism that could trigger self-reactive GC-Tfh cell/GC responses and autoimmunity via neighboring GC-Tfh cells.

scholarly journals Neoantigen driven B cell and CD4+ T follicular helper cell collaboration promotes robust anti-tumor CD8+ T cell responses

2020 ◽  
Author(s):  
Can Cui ◽  
Jiawei Wang ◽  
Ping-Min Chen ◽  
Kelli A. Connolly ◽  
Martina Damo ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cells ◽  
B Cell ◽  
Cell Interactions ◽  
Tumor Control ◽  
Cell Responses ◽  
Tfh Cells ◽  
Follicular Helper ◽  
T Follicular Helper Cell

AbstractCD4+ T follicular helper (TFH) cells provide help to B cells, which is critical for germinal center (GC) formation, but the importance of TFH-B cell interactions in cancer is unclear. We found TFH cells correlated with GC B cells and with prolonged survival of lung adenocarcinoma (LUAD) patients. To investigate further, we developed an LUAD model, in which tumor cells expressed B-cell- and T-cell-recognized neoantigens. Interactions between tumor-specific TFH and GC B cells were necessary for tumor control, as were effector CD8+ T cells. The latter were reduced in the absence of T cell-B cell interactions or the IL-21 receptor. IL-21 was produced primarily by TFH cells, development of which required B cells. Moreover, development of tumor-specific TFH cell-responses was also reliant upon tumors that expressed B-cell-recognized neoantigens. Thus, tumor-neoantigens themselves can control the fate decisions of tumor-specific CD4+ T cells by facilitating interactions with tumor-specific B cells.Abstract Figure

scholarly journals Preservation of Peripheral T Follicular Helper Cell Function in HIV Controllers

2017 ◽  
Vol 91 (14) ◽  
Author(s):  
Supranee Buranapraditkun ◽  
Franco Pissani ◽  
Jeffrey E. Teigler ◽  
Bruce T. Schultz ◽  
Galit Alter ◽  
...  
Keyword(s):  
T Cells ◽  
B Cells ◽  
B Cell ◽  
Cell Maturation ◽  
Elite Controllers ◽  
Follicular Helper ◽  
B Cell Maturation ◽  
B Cell Memory ◽  
Interleukin 21 ◽  
Hiv Controllers

ABSTRACT The maturation process of high-affinity antibodies is a result of intricate interactions between B cells and follicular helper T (Tfh) cells occurring in lymphoid germinal centers. HIV infection induces significant chronic immune activation, phenotypic skewing, and inflammation driven by years of continuous viral replication. High levels of viremia as well as immune activation and dysfunction have been demonstrated to have a perturbing impact on the B cell memory compartment and contribute to B cell exhaustion. Counterintuitively, the factors associated with perturbation of the B cell compartment seem to be favorable for the generation of highly affinity-matured Env-specific antibodies in a minority of HIV-infected individuals. Thus, the impact of HIV antigenemia on B cells and Tfh cell interactions warrants further exploration. We therefore studied immunophenotypes of HIV-specific B cells in individuals with differing levels of viral control using HIV Env gp120 probes and characterized the functionality of matched T cells in peripheral blood. While CXCR5+ CD4+ T cells were significantly diminished in HIV progressors, we found that a small subset of gp120-specific interleukin-21 (IL-21)-secreting CXCR5+ CD4+ T cells were significantly associated with gp120-specific B cell frequencies. In contrast, neither bulk CXCR5+ CD4+ T cells nor other HIV antigen specificities were associated with gp120-specific B cell levels. HIV-specific B cells derived from elite controllers displayed greater amounts of gp120-specific B cells in the resting memory subset, whereas HIV-specific B cells in progressors accumulated in tissue-like and activated memory subsets. Furthermore, CXCR5+ CD4+ T cells from elite controllers showed a stronger ex vivo capacity to induce B cell maturation and immunoglobulin class switching than cells from HIV progressors. IMPORTANCE Dissecting the factors that are involved in B cell maturation and antibody development is important for HIV vaccine design. In this study, we found that HIV Env-specific CXCR5+ CD4+ T cells that secrete interleukin-21 are strongly associated with B cell memory phenotypes and function. Moreover, we found that the immune responses of HIV controllers showed intrinsically better helper activity than those of HIV progressors.

Author response for "Dysregulation in B cell responses and T follicular helper cell function in ADA2 deficiency patients"

2020 ◽  
Author(s):  
Francesca Schena ◽  
Federica Penco ◽  
Stefano Volpi ◽  
Claudia Pastorino ◽  
Roberta Caorsi ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Function ◽  
Author Response ◽  
Helper Cell ◽  
Cell Responses ◽  
Follicular Helper ◽  
T Follicular Helper Cell ◽  
B Cell Responses
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