Autoreactive B Cell Differentiation in Diffuse Ectopic Lymphoid-Like Structures of Inflamed Pemphigus Lesions

Zhou, Shenjie; Liu, Zhicui; Yuan, Hsiao-Kuan; Zhao, Xiaoqing; Zou, Yaru; Zheng, Jie; Pan, Meng

doi:10.1016/j.jid.2019.07.717

Cited by 46 publications

(40 citation statements)

References 41 publications

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“…S4A), which generally last for a few days depending on the amount of autoantibody administered. These observations are consistent with previous analysis of skin samples of pemphigus patients (Furtado, 1959; Rados, 2011) and the recent description of lymphocyte infiltration at the lesion sites in patients (Yuan et al, 2017; Zhou et al, 2019). Therefore, the adoptive transfer of anti-Dsg1 antibodies is sufficient to initiate pemphigus in adult mice, in which the pathogenicity of anti-Dsg1 autoantibodies can be studied in the process of disease onset and resolution and in the context of an intact immune system.…”

Section: Resultssupporting

confidence: 93%

Distinct impact of IgG subclass and Fc-FcγR interaction on autoantibody pathogenicity in different IgG4-mediated diseases

Zhou

et al. 2020

Preprint

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IgG4 is the least potent human IgG subclass for the FcγR-mediated antibody effector function and is considered anti-inflammatory in the context of prolonged inflammation and allergic responses. Paradoxically, IgG4 is also the dominant IgG subclass of pathogenic autoantibodies in IgG4-mediated diseases. Here we show that the IgG subclass and Fc-FcγR interaction have a distinct impact on the pathogenic function of autoantibodies in different IgG4-mediated diseases. While IgG4 and its weak Fc-FcγR interaction have an ameliorative role in the pathogenicity of anti-ADAMTS13 autoantibodies isolated from thrombotic thrombocytopenic purpura (TTP) patients, they have an unexpected exacerbating effect on anti-Dsg1 autoantibody pathogenicity in pemphigus foliaceus (PF) models. Strikingly, a non-pathogenic anti-Dsg1 antibody variant optimized for FcγR-mediated effector function can attenuate the skin lesions induced by pathogenic anti-Dsg1 antibodies by promoting the clearance of dead keratinocytes. These studies suggest that IgG effector function contributes to the clearance of autoantibody-Ag complexes, which is harmful in TTP, but beneficial in PF and may provide new therapeutic opportunity.

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Section: Resultssupporting

confidence: 93%

Distinct impact of IgG subclass and Fc-FcγR interaction on autoantibody pathogenicity in different IgG4-mediated diseases

Zhou

et al. 2020

Preprint

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“…Once TLS are established, a milieu rich in survival factors, e.g., BLyS, IL-6, IL-7 and CXCL12 enables the persistence of incoming PCs and thus makes them inaccessible for systemic approaches of B cell depletion [124,125]. This finding is supported by a recent investigation of ectopic lymphoid-like structures in inflamed pemphigus lesions [112] and by the fact that isolated lymphocytes of lesional skin (as mentioned earlier) held the capacity to produce anti-desmoglein antibodies in vitro [37]. Of note, IL-22 and IL-17-mainly expressed by T cells-are also believed to play an important role in the formation or maintenance of TLS as they were shown to increase the expression of chemokines such as CXCL12 and CXCL13 in epithelial and/or stromal cells [126,127].…”

Section: Tls Formation and Associated Inflammatory Cytokinesmentioning

confidence: 82%

“…However, it needs to be further determined which phenotype of B cells is responsible for this feature. B cells have been shown to cluster in the dermis or participate in the formation of TLS [37,111,112]. These structures, consisting of other immune cells such as T cells, follicular dendritic cells and macrophages, stromal cells as well as several cytokines provided by the respective cells, might have the potential to create an appropriate micromilieu for skin-localized autoantigen-driven immune responses, as discussed below.…”

Section: Role Of B Cells As Apc In Autoimmunity and Their Potential Cmentioning

confidence: 99%

“…This is why TLS might be relevant not only in later stages of disease, but also in early phases when self-reactivity must be excluded via fully-functional control mechanisms. In the course of disease, TLS may act as a site of restimulation of memory lymphocytes or priming of precursors that boost differentiation and expansion of effector cells and maintain self-reactive inflammatory responses [112,124]. B cells can act as important APC in this regard and promote the expansion of Th cells [132].…”

Section: Tls Formation Provides a Niche For Local Autoimmunitymentioning

confidence: 99%

“…Proinflammatory cytokines are subsequently released from activated T cells and autoantibody production by PCs as well as immune complex formation are iniated [124]. TLS formation has been described in pemphigus and lupus erythematosus panniculitis, yet data concerning the appearance and specific role of TLS in autoimmune skin diseases are limited [111,112,133].…”

Section: Tls Formation Provides a Niche For Local Autoimmunitymentioning

confidence: 99%

See 2 more Smart Citations

Skin-Associated B Cells in the Pathogenesis of Cutaneous Autoimmune Diseases—Implications for Therapeutic Approaches

Fetter

Niebel

Braegelmann

et al. 2020

Cells

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B lymphocytes are crucial mediators of systemic immune responses and are known to be substantial in the pathogenesis of autoimmune diseases with cutaneous manifestations. Amongst them are lupus erythematosus, dermatomyositis, systemic sclerosis and psoriasis, and particularly those driven by autoantibodies such as pemphigus and pemphigoid. However, the concept of autoreactive skin-associated B cells, which may reside in the skin and locally contribute to chronic inflammation, is gradually evolving. These cells are believed to differ from B cells of primary and secondary lymphoid organs and may provide additional features besides autoantibody production, including cytokine expression and crosstalk to autoreactive T cells in an antigen-presenting manner. In chronically inflamed skin, B cells may appear in tertiary lymphoid structures. Those abnormal lymph node-like structures comprise a network of immune and stromal cells possibly enriched by vascular structures and thus constitute an ideal niche for local autoimmune responses. In this review, we describe current considerations of different B cell subsets and their assumed role in skin autoimmunity. Moreover, we discuss traditional and B cell-associated approaches for the treatment of autoimmune skin diseases, including drugs targeting B cells (e.g., CD19- and CD20-antibodies), plasma cells (e.g., proteasome inhibitors, CXCR4 antagonists), activated pathways (such as BTK- and PI3K-inhibitors) and associated activator molecules (BLyS, APRIL).

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We are memory: B‐cell responses in allergy and tolerance

2023

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The significance of B‐cell memory in sustaining IgE‐mediated allergies but also ensuring the development of long‐term allergen tolerance has remained enigmatic. However, well‐thought murine and human studies have begun to shed more light on this highly disputed subject. The present mini review highlights important aspects, like the involvement of IgG1 memory B cells, the meaning of low‐ or high‐affinity IgE antibody production, the impact of allergen immunotherapy, or the relevance of local memory established by ectopic lymphoid structures. Based on recent findings, future investigations should lead to deeper knowledge and the development of improved therapies treating allergic individuals.

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Autoreactive B Cell Differentiation in Diffuse Ectopic Lymphoid-Like Structures of Inflamed Pemphigus Lesions

Cited by 46 publications

References 41 publications

Distinct impact of IgG subclass and Fc-FcγR interaction on autoantibody pathogenicity in different IgG4-mediated diseases

Distinct impact of IgG subclass and Fc-FcγR interaction on autoantibody pathogenicity in different IgG4-mediated diseases

Skin-Associated B Cells in the Pathogenesis of Cutaneous Autoimmune Diseases—Implications for Therapeutic Approaches

We are memory: B‐cell responses in allergy and tolerance

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