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Identification and Characterization of Post-activated B Cells in Systemic Autoimmune Diseases.

ABSTRACT: Autoimmune diseases (AID) such as systemic lupus erythematosus (SLE), primary Sjögren's syndrome (pSS), and rheumatoid arthritis (RA) are chronic inflammatory diseases in which abnormalities of B cell function play a central role. Although it is widely accepted that autoimmune B cells are hyperactive in vivo, a full understanding of their functional status in AID has not been delineated. Here, we present a detailed analysis of the functional capabilities of AID B cells and dissect the mechanisms underlying altered B cell function. Upon BCR activation, decreased spleen tyrosine kinase (Syk) and Bruton's tyrosine kinase (Btk) phosphorylation was noted in AID memory B cells combined with constitutive co-localization of CD22 and protein tyrosine phosphatase (PTP) non-receptor type 6 (SHP-1) along with hyporesponsiveness to TLR9 signaling, a Syk-dependent response. Similar BCR hyporesponsiveness was also noted specifically in SLE CD27- B cells together with increased PTP activities and increased transcripts for PTPN2, PTPN11, PTPN22, PTPRC, and PTPRO in SLE B cells. Additional studies revealed that repetitive BCR stimulation of normal B cells can induce BCR hyporesponsiveness and that tissue-resident memory B cells from AID patients also exhibited decreased responsiveness immediately ex vivo, suggesting that the hyporesponsive status can be acquired by repeated exposure to autoantigen(s) in vivo. Functional studies to overcome B cell hyporesponsiveness revealed that CD40 co-stimulation increased BCR signaling, induced proliferation, and downregulated PTP expression (PTPN2, PTPN22, and receptor-type PTPs). The data support the conclusion that hyporesponsiveness of AID and especially SLE B cells results from chronic in vivo stimulation through the BCR without T cell help mediated by CD40-CD154 interaction and is manifested by decreased phosphorylation of BCR-related proximal signaling molecules and increased PTPs. The hyporesponsiveness of AID B cells is similar to a form of functional anergy.

SUBMITTER: Weißenberg SY

PROVIDER: S-EPMC6768969 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Identification and Characterization of Post-activated B Cells in Systemic Autoimmune Diseases.

Weißenberg Sarah Y SY Szelinski Franziska F Schrezenmeier Eva E Stefanski Ana-Luisa AL Wiedemann Annika A Rincon-Arevalo Hector H Welle Anna A Jungmann Annemarie A Nordström Karl K Walter Jörn J Imgenberg-Kreuz Juliana J Nordmark Gunnel G Rönnblom Lars L Bachali Prathyusha P Catalina Michelle D MD Grammer Amrie C AC Lipsky Peter E PE Lino Andreia C AC Dörner Thomas T

Frontiers in immunology 20190924

Autoimmune diseases (AID) such as systemic lupus erythematosus (SLE), primary Sjögren's syndrome (pSS), and rheumatoid arthritis (RA) are chronic inflammatory diseases in which abnormalities of B cell function play a central role. Although it is widely accepted that autoimmune B cells are hyperactive <i>in vivo</i>, a full understanding of their functional status in AID has not been delineated. Here, we present a detailed analysis of the functional capabilities of AID B cells and dissect the mec ...[more]

PMID: 31616406

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Project description:COVID-19 related infodemic is a threat to the successful COVID-19 vaccination campaigns. This might be especially apparent for patients with autoimmune diseases since there is no data available about the balance between benefits and risks of the newly developed COVID-19 vaccines in this population. We aim (i) to evaluate vaccine literacy skills in a population of patients with systemic autoimmune diseases, (ii) to examine the potential associations between vaccine literacy skills and sociodemographic characteristics and (iii) to analyze the relationships between attitudes, perceptions and beliefs about current vaccinations and vaccine literacy skills and sociodemographic characteristics. A cross-sectional study was conducted among 319 patients with systemic autoimmune diseases (92% females; 49.5% of patients in the 31-50 years age category). The vaccine literacy levels were determined using the Health Literacy about Vaccination in adulthood in Italian (HLVa-IT). Sociodemographic characteristics including gender, age, country and area of residence, civil status, socioeconomic status, educational attainment and occupational status were evaluated. The mean vaccine literacy functional and interactive-critical scores were 2.59 ± 0.74 and 3.07 ± 0.60, respectively. The vaccine literacy interactive-critical score was higher in females than in males (p = 0.048). Interactive-critical scores were associated with the area of residence, civil status and socioeconomic status, with the highest score in urban area of ≥ 100.000 inhabitants (p = 0.045), in widow patients (p = 0.023) and in patients with high socioeconomic status (p = 0.018). Significant differences were observed between the different education levels, for both the functional and the interactive-critical scores (p = 0.002 and p < 0.001, respectively), the highest score was observed in patients who completed a university degree. The level of vaccine literacy for functional and interactive-critical scales were medium. Area of residence, civil status and socioeconomic status represented determinants of vaccine literacy interactive-critical scale. Educational attainment also contributes to vaccine literacy functional scale. Insight into these factors is required to ensure an optimal vaccine literacy level in patients with autoimmune diseases.Supplementary informationThe online version contains supplementary material available at 10.1007/s12144-022-02713-y.

Dataset Information

Identification and Characterization of Post-activated B Cells in Systemic Autoimmune Diseases.

Publications

Identification and Characterization of Post-activated B Cells in Systemic Autoimmune Diseases.

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