Taurine (Tau) is a special sulphur-containing amino acid and has been widely used as a dietary supplement. Although Tau exists in lymphocytes in large quantities, the physiological significance of Tau to modulate human immunity is unknown. In the present study, we first found that Tau regulates the B-cell receptor (BCR)-mediated signal transduction and induces the B cells activation. The IgG production of mice after ovalbumin immunization was also increased by Tau administration. Moreover, the isothermal titration calorimetry and surface plasmon resonance analysis have shown that Tau specifically bound to the IgG2a-BCR. The Tau could bind to IgG F(ab\')2 regions via fluorescence spectroscopy analysis. In the molecular docking analysis, Tau bound to the framework regions (FRs) of variable region of the heavy chains (VH ) and in the light chains (VL ) of IgG2a-BCR. Our results suggested that Tau could improve the activation of B cells by interaction with the VH /VL FRs of BCR.

The humoral response requires rapid growth, biosynthetic capacity, proliferation and differentiation of B cells. These processes involve profound B-cell phenotypic transitions that are coupled to drastic changes in metabolism so as to meet the extremely different energetic requirements as B cells switch from resting to an activated, highly proliferative state and to plasma or memory cell fates. Thus, B cells execute a multi-step, energetically dynamic process of profound metabolic rewiring from low ATP production to transient and large increments of energy expenditure that depend on high uptake and consumption of glucose and fatty acids. Such metabolic plasticity is under tight transcriptional and post-transcriptional regulation. Alterations in B-cell metabolism driven by genetic mutations or by extrinsic insults impair B-cell functions and differentiation and may underlie the anomalous behavior of pathological B cells. Herein, we review molecular switches that control B-cell metabolism and fuel utilization, as well as the emerging awareness of the impact of dynamic metabolic adaptations of B cells throughout the different phases of the humoral response.

UNASSIGNED: For mechanistic studies, in-vitro human B-cell differentiation and generation of plasma cells are invaluable techniques. However, the heterogeneity of both T-cell-dependent (TD) and T-cell-independent (TI) stimuli and the disparity of culture conditions used in existing protocols make the interpretation of results challenging. The aim of the present study was to achieve the most optimal B-cell differentiation conditions using isolated CD19+ B cells and peripheral blood mononuclear cell (PBMC) cultures. We addressed multiple seeding densities, different durations of culturing, and various combinations of TD and TI stimuli including B-cell receptor (BCR) triggering. B-cell expansion, proliferation, and differentiation were analyzed after 6 and 9 days by measuring B-cell proliferation and expansion, plasmablast and plasma cell formation, and immunoglobulin (Ig) secretion. In addition, these conditions were extrapolated using cryopreserved cells and differentiation potential was compared.
UNASSIGNED: This study demonstrates improved differentiation efficiency after 9 days of culturing for both B-cells and PBMC cultures using CD40L and IL-21 as TD stimuli and 6 days for CpG and IL-2 as TI stimuli. We arrived at optimized protocols requiring 2,500 and 25,000 B-cells per culture well for the TD and TI assays, respectively. The results of the PBMC cultures were highly comparable to the B-cell cultures, which allows dismissal of additional B-cell isolation steps prior to culturing. In these optimized TD conditions, the addition of anti-BCR showed a little effect on phenotypic B-cell differentiation; however, it interferes with Ig secretion measurements. The addition of IL-4 to the TD stimuli showed significantly lower Ig secretion. The addition of BAFF to optimized TI conditions showed enhanced B-cell differentiation and Ig secretion in B-cell but not in PBMC cultures. With this approach, efficient B-cell differentiation and Ig secretion were accomplished when starting from fresh or cryopreserved samples.
UNASSIGNED: Our methodology demonstrates optimized TD and TI stimulation protocols for more in-depth analysis of B-cell differentiation in primary human B-cell and PBMC cultures while requiring low amounts of B cells, making them ideally suited for future clinical and research studies on B-cell differentiation of patient samples from different cohorts of B-cell-mediated diseases.

Primary Sjögren\'s Syndrome (pSS) carries the highest risk for non-Hodgkin\'s lymphoma (NHL) development among systemic autoimmune diseases. However, the paucity of data on the long-term survival of those patients and the lack of established predictors for each lymphoma histologic subtype prompted our present study.
We retrospectively analysed 121 patients diagnosed with NHL according to the WHO classification criteria. All patients fulfilled the 2016 ACR-EULAR classification criteria for pSS. Cumulative clinical, laboratory, radiologic, treatment regimens and histologic data were recorded, harmonized and analysed. Overall survival (OS) and event-free survival (EFS) curves were calculated. A mucosa-associated lymphoid tissue lymphoma (MALTL) prediction model was developed by applying innovative data-driven analysis of clinical features present at the time of pSS diagnosis.
MALTLs constituted the majority of lymphomas (92/121, 76.0%) followed by diffuse large B-cell lymphomas (DLBCL) (11/121, 9.0%) and nodal marginal zone lymphomas (NMZL) (8/121, 7%). MALTLs show salivary glands localization, limited disease and often bone marrow and nodal involvement. The 10-year OS and EFS rates were 79% and 45.5% for MALTLs, 40.9% and 24.2% for DLBCL and 46% and 31% for NMZL. Cryoglobulinemia, focus score and the total EULAR SS Disease Activity Index (ESSDAI) composite index at pSS diagnosis were proven independent MALTL predictors. Even though MALTLs have a comparatively good survival outlook, they are accompanied by frequent events throughout their clinical course.
Common features of pSS, present at diagnosis, can predict future lymphomagenesis meriting a more intensive follow-up plan.

Chronic discoid lupus erythematosus (CDLE) is the most common subtype of chronic cutaneous lupus erythematosus (CCLE), and may be associated with systemic lupus manifestations1 . Type I interferons (IFNs) have been identified to play a key role in its pathogenesis2,3 . Following exposure to nuclear components (such as endogenous nucleic acid) released by cellular damage, plasmacytoid dendritic cells (pDC) and keratinocytes inadequately produce type I IFN. In an autocrine loop manner IFNs will bind to IFN-α/β receptors and will activate Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway, thus enhancing expression of proinflammatory mediators (e.g., CXCL10)2,4 .