Increased frequency of circulating follicular helper T cells in lupus patients is associated with autoantibody production in a CD40L-dependent manner

Xu, Huaheng; Liu, Jing; Cui, Xiufang; Zuo, Yanhua; Zhang, Zongfang; Li, Yanxia; Tao, Ran; Liu, Ying; Pang, Jie

doi:10.1016/j.cellimm.2015.01.014

Cited by 52 publications

(56 citation statements)

References 28 publications

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“…In addition these cells have been found in lymphoid aggregates and ectopic germinal centers in lupus nephritis lesions expressing ICOS, PD-1, Bcl-6 and IL-21 [40]. Induction of B cell differentiation into plasmablasts depends on CD40L but not on ICOS expression in T FH [25]. However, ICOS signaling, as well as OX40, through p110δ, are necessary for T FH differentiation [41,42].…”

Section: Extrafollicular T Cells Help B Cells To Produce Autoantibodimentioning

confidence: 99%

T cells in Systemic Lupus Erythematosus

Suárez‐Fueyo

Bradley

Tsokos

2016

Current Opinion in Immunology

166

127

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Systemic Lupus Erythematosus is an autoimmune disorder caused by a complex combination of genetic, epigenetic and environmental factors. Different polymorphisms and epigenetic modifications lead to altered gene expression and function of several molecules which lead to abnormal T cell responses. Metabolic and functional alterations result in peripheral tolerance failures and biased differentiation of T cells into pro-inflammatory and B cell-helper phenotypes as well as the accumulation of disease-promoting memory T cells. Understanding these T cell alterations and their origins is necessary to develop more accurate patient classification systems and to discover new therapeutic targets.

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Section: Extrafollicular T Cells Help B Cells To Produce Autoantibodimentioning

confidence: 99%

T cells in Systemic Lupus Erythematosus

Suárez‐Fueyo

Bradley

Tsokos

2016

Current Opinion in Immunology

166

127

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“…CXCR5 endows lymphocytes with the capacity to migrate to B cell follicles rich in C-X-C motif chemokine ligand 13 (CXCL13) [7,8]. Tfh cells motility is also regulated by ICOS-ICOS-L (Inducible T-cell Costimulator) interactions between Tfh cells and non-cognate B cells at the T-B border, which potentiates Tfh cells migration into the follicle [9]. Once in the follicle, Tfh cells activity depends on cognate interactions with B cells, which further reinforces Tfh cells differentiation and function [9,10].…”

Section: Introductionmentioning

confidence: 99%

T follicular helper cells regulate the activation of B lymphocytes and antibody production during Plasmodium vivax infection

et al. 2017

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Although the importance of humoral immunity to malaria has been established, factors that control antibody production are poorly understood. Follicular helper T cells (Tfh cells) are pivotal for generating high-affinity, long-lived antibody responses. While it has been proposed that expansion of antigen-specific Tfh cells, interleukin (IL) 21 production and robust germinal center formation are associated with protection against malaria in mice, whether Tfh cells are found during Plasmodium vivax (P. vivax) infection and if they play a role during disease remains unknown. Our goal was to define the role of Tfh cells during P. vivax malaria. We demonstrate that P. vivax infection triggers IL-21 production and an increase in Tfh cells (PD-1+ICOS+CXCR5+CD45RO+CD4+CD3+). As expected, FACS-sorted Tfh cells, the primary source of IL-21, induced immunoglobulin production by purified naïve B cells. Furthermore, we found that P. vivax infection alters the B cell compartment and these alterations were dependent on the number of previous infections. First exposure leads to increased proportions of activated and atypical memory B cells and decreased frequencies of classical memory B cells, whereas patients that experienced multiple episodes displayed lower proportions of atypical B cells and higher frequencies of classical memory B cells. Despite the limited sample size, but consistent with the latter finding, the data suggest that patients who had more than five infections harbored more Tfh cells and produce more specific antibodies. P. vivax infection triggers IL-21 production by Tfh that impact B cell responses in humans.

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“…Considering the important role of TFH in B cells selection, functional status of TFH would contribute to autoreactive B cells escaping into circulation [113,115,116]. Increased numbers of TFH and its association with autoantibody production have been reported in SLE patients and mice [117][118][119]. IL-21, as one of the signature molecules of TFH, is up-regulated in SLE and leads to expansion of TFH [120][121][122].…”

Section: B Cell Tolerance Checkpointsmentioning

confidence: 99%

B cells biology in systemic lupus erythematosus—from bench to bedside

Zhang

2015

Sci. China Life Sci.

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Systemic lupus erythematosus (SLE) is a debilitating autoimmune disease that can involve multi-organs. B cells play a central role in the immunopathogenesis via antibody-dependent and antibody-independent ways. Excessive autoantibodies production, hyperresponsiveness and prolonged survival of autoreactive B cells are characteristics of SLE. In this article, mechanisms of self-tolerance loss of B cells and promising B cell-targeting therapies in lupus are reviewed and discussed. Systemic lupus erythematosus (SLE), the paradigm of autoimmune disease with the underlying mechanisms involving multiple immunological abnormalities, is a severely debilitating disease with multi-organ involvement and diverse autoantibodies spectrum [1]. Among the multiple elements in the pathogenesis, B cells play a central role in SLE through antibody dependent and independent manners [2]. Presence of pathogenic autoantibodies is not only the hallmark of SLE and the clue for diagnosis, but also associated with characteristic pathological injury and specific clinical manifestations [3][4][5]. In addition, the pathogenic role of B cells is also attributed to its antibody independent functions, including but not limited to antigen presentation, T cell crosstalk, dendritic cells (DCs) recruitment, pro-inflammatory cytokine secretion. Why and how auto-reactive B cells in lupus lose self-tolerance, escape from central and peripheral checkpoints, become over-activated and spontaneously produce autoantibodies, are always the focus of clinical and basic research. Therefore, it is important to summarize our current knowledge about the underlying mechanisms of self-tolerance breakdown and pathogenic functioning pathways of B cells in SLE. So we review here about B cell biology in SLE, including its differentiation and selection, functioning and signaling, surviving and apoptosis, and the resulting potential therapeutic targets both in mice and human lupus.

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Increased frequency of circulating follicular helper T cells in lupus patients is associated with autoantibody production in a CD40L-dependent manner

Cited by 52 publications

References 28 publications

T cells in Systemic Lupus Erythematosus

T cells in Systemic Lupus Erythematosus

T follicular helper cells regulate the activation of B lymphocytes and antibody production during Plasmodium vivax infection

B cells biology in systemic lupus erythematosus—from bench to bedside

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