Phenotypic, transcriptomic, and spatial characterization of CD45RB naïve mature B cells: Implications in Sjögren's disease.

The conventional classification of mature B cells overlooks the diversity within IgD CD27 naïve B cells. Here, to identify distinct mature naïve B cells, we categorized CD45RB B cells (NA RB-) and CD45RB B cells (NA RB+) and explore their function and localization in circulation and tissues under physiological and pathological conditions. NA RB+ B cells, found in secondary lymphoid organs, differentiate into plasmablasts and secrete IgM.

Maf expression in B cells restricts reactive plasmablast and germinal center B cell expansion.

Precise regulation of B cell differentiation is essential for an effective adaptive immune response. Here, we show that B cell development in mice with B cell-specific Maf deletion is unaffected, but marginal zone B cells, germinal centre B cells, and plasmablasts are significantly more frequent in the spleen of naive Maf-deficient mice compared to wild type controls. In the context of a T cell-dependent immunization, Maf deletion causes increased proliferation of germinal centre B cells and extrafollicular plasmablasts.

Tolerance to intraoral biofilms and their effectiveness in improving mouth dryness and modifying oral microbiota in patients with primary Sjögren's syndrome: "Predelfi study".

Introduction: Primary Sjögren's syndrome (pSS) is a systemic autoimmune disease characterized by exocrine gland dysfunction. No therapeutic strategy is sufficient on its own for the management of dry mouth and therapeutic innovations are required.

Methods: This Predelfi study was a single-center, prospective, comparative, randomized, double-blind, cross-over controlled study with the primary objective of assessing the tolerance to and effectiveness of two adhesive biofilms (containing prebiotics and, sodium alginate, respectively) in patients with pSS and hyposialia (#NCT04206826 in ClinicalTrials.

Untargeted Metabolomic Approach to Study the Impact of Aging on Salivary Metabolome in Women.

Despite the growing interest in salivary metabolomics, few studies have investigated the impact of aging on the salivary metabolome. The alterations in metabolic pathways that occur with aging are likely to be observed in pathologies affecting older people and may interfere with the search for salivary biomarkers. It is therefore important to investigate the age-related changes occurring in the salivary metabolome.

Molecular Mechanisms Driving IL-10- Producing B Cells Functions: STAT3 and c-MAF as Underestimated Central Key Regulators?

Regulatory B cells (Bregs) have been highlighted in very different pathology settings including autoimmune diseases, allergy, graft rejection, and cancer. Improving tools for the characterization of Bregs has become the main objective especially in humans. Transitional, mature B cells and plasma cells can differentiate into IL-10 producing Bregs in both mice and humans, suggesting that Bregs are not derived from unique precursors but may arise from different competent progenitors at unrestricted development stages.

Treatment of Sjögren's Syndrome with Mesenchymal Stem Cells: A Systematic Review.

Mesenchymal stem cells (MSCs) are ubiquitous in the human body. Mesenchymal stem cells were initially isolated from bone marrow and later from other organs such as fatty tissues, umbilical cords, and gingiva. Their secretory capacities give them interesting immunomodulatory properties in cell therapy.

The diversity of the plasmablast signature across species and experimental conditions: A meta-analysis.

Antibody-secreting cells (ASC) are divided into two principal subsets, including the long-lived plasma cell (PC) subset residing in the bone marrow and the short-lived subset, also called plasmablast (PB). PB are described as a proliferating subset circulating through the blood and ending its differentiation in tissues. Due to their inherent heterogeneity, the molecular signature of PB is not fully established.

A Proinflammatory Cytokine Network Profile in Th1/Type 1 Effector B Cells Delineates a Common Group of Patients in Four Systemic Autoimmune Diseases.

Objective: The effector T cell and B cell cytokine networks have been implicated in the pathogenesis of systemic autoimmune diseases, but the association of these cytokine networks with the heterogeneity of clinical manifestations and immune profiles has not been carefully examined. This study was undertaken to examine whether cytokine profiles can delineate distinct groups of patients in 4 systemic autoimmune diseases (systemic lupus erythematosus, Sjögren's syndrome, rheumatoid arthritis, and systemic sclerosis).

Methods: A total of 179 patients and 48 healthy volunteers were enrolled in the multicenter cross-sectional PRECISE Systemic Autoimmune Diseases (PRECISESADS) study.

Keratinocytes Communicate with Sensory Neurons via Synaptic-like Contacts.

Objective: Pain, temperature, and itch are conventionally thought to be exclusively transduced by the intraepidermal nerve endings. Although recent studies have shown that epidermal keratinocytes also participate in sensory transduction, the mechanism underlying keratinocyte communication with intraepidermal nerve endings remains poorly understood. We sought to demonstrate the synaptic character of the contacts between keratinocytes and sensory neurons and their involvement in sensory communication between keratinocytes and sensory neurons.

Innate B Cells: the Archetype of Protective Immune Cells.

The innate B cell (IBC) population is heterogeneous and involved in the primary immune response. IBC functions include a high ability to produce natural antibodies with IgM isotype, the elimination of apoptotic cells, and a capacity to be cognate help to T cells. Among IBC subsets, B-1 cells and marginal zone B cells are the main producers of IgM, act as rapid immune responders that may relocate to follicular lymphoid and differentiate to cytokine and antibody-secreting cells shortly after infection.

B cells in Sjögren's syndrome: from pathophysiology to therapeutic target.

Biological abnormalities associated with B lymphocytes are a hallmark of patients with primary Sjögren's syndrome. Those patients present abnormal distribution of B lymphocytes in peripheral blood and B cells in exocrine glands. B cells produce auto-antibodies, cytokines and present antigens but can also suppressive functions.

Assessment of major salivary gland size in primary Sjögren's syndrome: Comparison between clinical examination and ultrasonography.

Objective: Parotidomegaly is a criterion of the EULAR Primary Sjögren Syndrome Disease Activity Index (ESSDAI). The cut-off value was set at 3 cm in length for the parotid gland, 2 cm for the submandibular glands. However, clinical appreciation of salivary glands size remains hazardous.

In-depth characterization of CD24(high)CD38(high) transitional human B cells reveals different regulatory profiles.

Background: CD24(high)CD38(high) transitional B cells represent cells at a key stage in their developmental pathway. In addition, these B cells have been widely ascribed regulatory functions and involvement in the control of chronic inflammatory diseases. However, the phenotypic and functional overlap between these cells and regulatory B cells remains controversial.

Specific forms of BAFF favor BAFF receptor-mediated epithelial cell survival.

Although B cell activating factor (BAFF) and its receptor BR3 are produced and expressed by many cells, their role has been restricted to the lymphocyte lineage. Using various techniques (RT-PCR, indirect immunofluorescence, flow cytometry analysis), we observed the expression of BR3 and the production of BAFF by the human salivary gland cell line, by epithelial cells from biopsies of Sjögren's syndrome patients and their controls, but also by salivary gland epithelial cells in culture. To decipher the role of BAFF and BR3 on epithelial cells, BAFF and BR3 were neutralized by blocking antibodies or RNA specific inhibitor (siBR3) and epithelial cell survival was analyzed.

Diagnostic criteria for autoimmune neutropenia.

Autoimmune neutropenia denotes that the number of circulating polymorphonuclear neutrophils is below 1.5×10(9)/L. This encompasses a wide range of disorders from primary conditions to complications of systemic autoimmune diseases or hematological neoplasms.

Importance of Toll-like receptors for B lymphocyte survival in primary Sjögren's syndrome.

The Sjögren's syndrome is a systemic autoimmune disease characterized by lymphocytic infiltration of the glands responsible for mouth and eyes dryness. A minority of infiltrating B cells is organized as germinal centers while the majority is aggregated into clusters of transitional and marginal zone B cells. The Toll-like receptor 9 (TLR9) recognizes microbial DNA but also, sometimes, the self DNA.

The complexity of the BAFF TNF-family members: implications for autoimmunity.

The B-cell activating factor belonging to the tumor-necrosis factor family BAFF contributes to autoimmune disorders. As such, BAFF might become a therapeutic target. However, this molecule has pleiotropic effects that are as numerous as they are varied.

Role of Toll-like receptors in primary Sjögren's syndrome with a special emphasis on B-cell maturation within exocrine tissues.

Be they follicular cells within the germinal centers (GCs) or marginal zone (MZ), all naïve mature B lymphocytes need tonic signaling to stay alive. We reasoned that the same holds true for those B lymphocytes that proliferate in the salivary glands (SGs) of patients with primary Sjögren's syndrome. Based on B cell infiltration, 11 SGs and three tonsil samples were selected for further examination.

Colocalization of Porphyromonas gingivalis with CD4+ T cells in periodontal disease.

Porphyromonas gingivalis, an anaerobic, asaccharolytic gram-negative bacterium, is a causative agent in chronic periodontitis. It has many virulence factors that facilitate infection of the gingiva, but little is known about the local immune cells that respond to this bacterium. The aims of this study were to quantify P.

B-cell tolerance breakdown in Sjögren's syndrome: focus on BAFF.

Sjögren's syndrome (SS) is an autoimmune epithelitis hallmarked by a destruction of epithelial cells, the subsequent lymphocytic infiltration of exocrine glands and their ensuing dryness. Given the prominent role currently assigned to B cells in SS, it is not surprising that the B cell activating factor belonging to the Tumor Necrosis Factor family (BAFF) is involved in its pathogenesis. When overexpressed, this cytokine leads to self-reactive B cells emergence at the transitional B-cell stage.

New ELISA for B cell-activating factor.

Background: The B cell-activating factor of the TNF family (BAFF) is upregulated in autoimmune diseases, but a number of conflicting results have cast doubts on the reliability of the ELISA protocols currently used for its quantification. This situation led us to develop a new ELISA for the measurement of BAFF.

Methods: BAFF was purified for use alongside nonglycosylated recombinant BAFF.

Ectopic germinal centers are rare in Sjogren's syndrome salivary glands and do not exclude autoreactive B cells.

This study reports on the characterization of B cells of germinal center (GC)-like structures infiltrating the salivary glands (SGs) of patients with Sjögren's syndrome. Eight two-color combinations were devised to characterize the phenotype of these B cells in 11 SG specimens selected from biopsies obtained from 40 Sjögren's syndrome patients and three normal tonsils. The 9G4 mAb, which recognizes V4.

Does the BAFF dysregulation play a major role in the pathogenesis of systemic lupus erythematosus?

Given the prominent role currently assigned to B lymphocytes in systemic lupus erythematosus, it is not surprising that the B cell activity factor belonging to the tumor necrosis factor family (BAFF) is involved in its pathogenesis. This cytokine is produced in excess, and inserted into its receptors on the surface of circulating B cells. Up-regulation of BAFF is most likely to lead to breach of tolerance by aberrant survival of B cells directed to the self.

Intravenous immunoglobulin and cytokines: focus on tumor necrosis factor family members BAFF and APRIL.

The presence of natural autoantibodies against cytokines has been reported in healthy individuals. Because circulating cytokines may be implicated in the clinical outcome of numerous diseases, the mode of action of intravenous immunoglobulin (IVIg) (pooled from sera over a thousand normal individuals) may involve immunomodulation of the cytokine network. We review the anti-cytokine effects of IVIg as well as the consequences of IVIg infusions on cytokine production.