The signalling pathways, calcineurin B-like protein 5 (CBL5)-CBL-interacting protein kinase 8 (CIPK8)/CIPK24-salt overly sensitive 1 (SOS1), transduce salt signals in seed germination in Arabidopsis.

For plant growth under salt stress, sensing and transducing salt signals are central to cellular Na+ homoeostasis. The calcineurin B-like protein (CBL)-CBL-interacting protein kinase (CIPK) complexes play critical roles in transducing salt signals in plants. Here, we show that CBL5, an ortholog of CBL4 and CBL10 in Arabidopsis, interacts with and recruits CIPK8/CIPK24 to the plasma membrane. Yeast cells coexpressing CBL5, CIPK8/CIPK24 and SOS1 demonstrated lesser Na+ accumulation and a better growth phenotype than the untransformed or SOS1 transgenic yeast cells under salinity. Overexpression of CBL5 improved the growth of the cipk8 or cipk24 single mutant but not the cipk8 cipk24 double mutant under salt stress, suggesting that CIPK8 and CIPK24 were the downstream targets of CBL5. Interestingly, seed germination in cbl5 was severely inhibited by NaCl, which was recovered by the overexpression of CBL5. Furthermore, CBL5 was mainly expressed in the cotyledons and hypocotyls, which are essential to seed germination. Na+ efflux activity in the hypocotyls of cbl5 was reduced relative to the wild-type under salt stress, enhancing Na+ accumulation. These findings indicate that CBL5 functions in seed germination and protects seeds and germinating seedlings from salt stress through the CBL5-CIPK8/CIPK24-SOS1 pathways.

Leisure-time physical activity and the incidence of atrial fibrillation in senior adults: a prospective cohort study.

OBJECTIVE: Whether physical activity could reduce the risk of atrial fibrillation (AF) remains unclear. This study was to investigate the relationship of leisure-time physical activity (LTPA) with AF incidence among Chinese older adults. METHODS: A total of 3253 participants aged ≥60 years from the Guangzhou Heart Study were successfully followed between March 2018 and September 2019. LTPA was assessed using a modified Global Physical Activity Questionnaire. AF was ascertained by 12-lead electrocardiograms, 24-hour single-lead Holter and clinical examination. The Cox proportional hazards model was used to the estimate hazard ratio (HR) and 95% confidence interval (CI) after adjustment for confounders, and the population-attributable fraction (PAF) was estimated. RESULTS: A total of 76 (2.34%) new-onset cases of AF were identified during a median of 31.13 months of follow-up. After adjustment for confounders, subjects who had LTPA at least 10.0 metabolic equivalent (MET)-hours/week had a 55% lower risk of developing AF (HR: 0.45, 95%CI: 0.25-0.81), and at least 20 MET-hours/week reduced the risk by 45% (HR: 0.55, 95%CI: 0.34-0.92). At least 11% (PAF: 11%, 95%CI: 0%-20%) or 14% (PAF: 14%, 95%CI: 0%-26%) of AF cases could be avoided, respectively, if the subjects do LTPA at least 10 MET-hours/week or 20 MET-hours/week. A significant exposure-response trend was also observed between LTPA and AF risk (Plinear-trend = 0.002). For a specific LTPA, doing housework was associated with a 43% reduced risk, while engaging in ball games was associated with an increased risk. CONCLUSION: This prospective cohort study indicated that a higher LTPA volume was associated with a lower AF risk in Chinese older adults.

Short-term and long-term efficacy of sublingual immunotherapy in different courses for house dust mite-induced allergic rhinitis.

PURPOSE: Sublingual immunotherapy (SLIT) has been proven to be an effective and safe treatment for patients with house dust mite (HDM)-induced allergic rhinitis (AR) to achieve short-term and long-term efficacy. This study aimed to investigate the relationship between SLIT duration and long-term efficacy. MATERIALS AND METHODS: This study involved 134 patients who underwent SLIT between 2019 and 2021 (in the 2-year group), between 2018 and 2021(in the 3-year group), or between 2017 and 2021 (in the 4-year group). The total nasal symptoms score (TNSS), total medication score (TMS), visual analogue scale (VAS), the Mini Rhinoconjunctivitis Quality of Life Questionnaire (MiniRQLQ) and adverse events (AEs) were assessed at baseline, after treatment (2021) and one year after the treatment completion (2022). The correlation between MiniRQLQ and other indicators was also analyzed. RESULTS: After SLIT, patients in all three groups showed significant improvements in TNSS, TMS, VAS and MiniRQLQ scores (all p < 0.001). These improvements were sustained even one year after SLIT. Patients who received 3-4 years of SLIT showed significant improvement compared with those who received 2 years of SLIT in all clinical outcomes (all p < 0.01). The analysis showed positive correlations between the MiniRQLQ and TNSS, TMS, and VAS (all p < 0.001). No significant difference was observed in the AE rate in all three groups (p > 0.05). CONCLUSION: Different duration of HDM SLIT could generate various short-term and long-term clinical efficacy. The MiniRQLQ could be applied to evaluate SLIT efficacy in clinical practice.

Nickel-Catalyzed Reductive [4 + 1] Sila-Cycloaddition of 1,3-Dienes with Dichlorosilanes.

Transition-metal-catalyzed sila-cycloaddition has been a promising tool for accessing silacarbocycle derivatives, but the approach has been limited to a selection of well-defined sila-synthons. Herein, we demonstrate the potential of chlorosilanes, which are industrial feedstock chemicals, for this type of reaction under reductive nickel catalysis. This work extends the scope of reductive coupling from carbocycle to silacarbocycle synthesis and from single C-Si bond formation to sila-cycloaddition reactions. The reaction proceeds under mild conditions and shows good substrate scope and functionality tolerance, and it offers new access to silacyclopent-3-enes and spiro silacarbocycles. The optical properties of several spiro dithienosiloles as well as structural variations of the products are demonstrated.

Plastid KEA-type cation/H+ antiporters are required for vacuolar protein trafficking in Arabidopsis.

Arabidopsis plastid antiporters KEA1 and KEA2 are critical for plastid development, photosynthetic efficiency, and plant development. Here, we show that KEA1 and KEA2 are involved in vacuolar protein trafficking. Genetic analyses found that the kea1 kea2 mutants had short siliques, small seeds, and short seedlings. Molecular and biochemical assays showed that seed storage proteins were missorted out of the cell and the precursor proteins were accumulated in kea1 kea2. Protein storage vacuoles (PSVs) were smaller in kea1 kea2. Further analyses showed that endosomal trafficking in kea1 kea2 was compromised. Vacuolar sorting receptor 1 (VSR1) subcellular localizations, VSR-cargo interactions, and p24 distribution on the endoplasmic reticulum (ER) and Golgi apparatus were affected in kea1 kea2. Moreover, plastid stromule growth was reduced and plastid association with the endomembrane compartments was disrupted in kea1 kea2. Stromule growth was regulated by the cellular pH and K+ homeostasis maintained by KEA1 and KEA2. The organellar pH along the trafficking pathway was altered in kea1 kea2. Overall, KEA1 and KEA2 regulate vacuolar trafficking by controlling the function of plastid stromules via adjusting pH and K+ homeostasis.

Nickel-Catalyzed Cross-Electrophile 1,2-Silyl-Arylation of 1,3-Dienes with Chlorosilanes and Aryl Bromides.

Catalytic, three-component, cross-electrophile reactions have recently emerged as a promising tool for molecular diversification, but studies have focused mainly on the alkyl-carbonations of alkenes. Herein, the scope of this method has been extended to conjugated dienes and silicon chemistry through silylative difunctionalization of 1,3-dienes with chlorosilanes and aryl bromides. The reaction proceeds under mild conditions to afford 1,2-linear-silylated products, a selectivity that is different to those obtained from conventional methods via an intermediary of H(C)-η3 -π-allylmetal species. Preliminary mechanistic studies reveal that chlorosilane reacts with 1,3-diene first and then couples with aryl bromide.

[Effects of Yishen Tongluo Prescription on the PI3K-Akt-MTOR pathway and the protein and mRNA expressions of CatSper-1 and HSPA2 in the testis tissue of oligoasthenospermia rats].

OBJECTIVE: To study the effect of Yishen Tongluo Prescription (YTP) on the testis tissue of the male rats with oligoasthenospermia (OAS) and its action mechanism based on the PI3K-AKT-mTOR pathway. METHODS: We randomly divided 48 SPF male SD rats into 8 groups: normal control, OAS model control, L-carnitine (LC), high-dose YTP, low-dose YTP, Omipalisib inhibitor (OI), OI + high-dose YTP, and OI + low-dose YTP, with 6 rats in each group. We established a model of OAS in the latter 7 groups by intragastric administration of tripterygium wilfordii polyside, followed by intervention with corresponding drugs. After treatment, we obtained semen parameters from the rats, observed pathological changes in the testis tissue by HE staining, and determined the expressions of the PI3K-AKT-mTOR signaling pathway-related proteins and mRNA by Western blot and real-time fluorescence quantitative PCR (qRT-PCR). RESULTS: Sperm concentration and total sperm motility were significantly improved in the LC and YTP groups compared with those in the OAS model control group (P < 0.001). HE staining showed irregularly arranged spermatogenic cells and narrowed lumina and widened gaps of seminiferous tubules in the OAS model controls, as well as similar pathological changes in the LC, YTP and OI + YTP groups. Significant up-regulation was observed in the protein expressions of p-Akt, CatSper-1 and HSPA2 in the LC group (P < 0.05), those of p-Akt, mTOR, catsper-1 and HSP2 in the low-dose YTP group (P < 0.05) and that of PI3K in the high-dose YTP group (P < 0.05) compared with those in the model controls. There were no statistically significant differences in the expressions of PI3K, mTOR and catsper-1 between the OI and model control groups (P > 0.05), nor in those of PI3K, p-Akt, mTOR, CatSper-1 and HSPA2 between the OI + YTP and the former two groups (P > 0.05). The mRNA expressions of PI3K, mTOR, CatSper-1 and HSPA2 were remarkably higher in the LC and YTP groups than in the model control (P< 0.05), with those of catsper-1 and PI3K even more significantly up-regulated in the high-dose than in the low-dose YTP group (P< 0.001; P< 0.05). Statistically significant differences were not observed in the mRNA expressions of PI3K, mTOR, CatSper-1 and HSPA2 between the model control and OI groups (P > 0.05), nor in those of PI3K, mTOR, catsper-1 and HSPA2 between the model control and OI + YTP groups (P > 0.05). CONCLUSION: Yishen Tongluo Prescription can improve sperm quality and pathological changes of the testis tissue in rats with Tripterygium glycoside-induced OAS, which might be attributed to its ability of up-regulating the expressions of the PI3K Akt mTOR pathway-related proteins and mRNA in the testis tissue.

A Fully Distributed Protocol with an Event-Triggered Communication Strategy for Second-Order Multi-Agent Systems Consensus with Nonlinear Dynamics.

This paper presents the communication strategy for second-order multi-agent systems with nonlinear dynamics. To address the problem of the scarcity of communication channel resources and get rid of using continuous signals among the followers in lead-follower multi-agent systems, a novel event-triggered communication mechanism is proposed in this paper. To avoid employing the centralized information that depends on the Laplacian matrix spectrum, a network protocol with updated coupling gains is proposed, as well as an event-triggered strategy with updated thresholds. To eliminate the ill effects of inter-node communicating noise, relative positions are employed by the protocol instead of absolute positions. By a Lyapunov-Krasovskii functional, it is rigorously proven that the leader-following consensus of MASs is achieved without Zeno behavior, under the control of the proposed protocol with an event-triggered mechanism communication. The effectiveness of the proposed protocol is verified through numerical examples.

Dexrazoxane ameliorates doxorubicin-induced cardiotoxicity by inhibiting both apoptosis and necroptosis in cardiomyocytes.

Doxorubicin, as a first line chemotherapeutic agent, its usage is limited owing to cardiotoxicity. Necroptosis is a new form of programmed cell death, and recent investigations indicated that necroptosis is vitally involved in serious cardiac pathological conditions. Dexrazoxane is the only cardiac protective drug approved by FDA for anthracycline. We aimed to explore whether and how dexrazoxane regulates doxorubicin-induced cardiomyocyte necroptosis. First, doxorubicin could cause heart failure and reduce cardiomyocyte viability by promoting cell apoptosis and necroptosis in vivo and in vitro. Second, necroptosis plays an important role in doxorubicin induced cardiomyocyte injury, which could be inhibited by Nec-1. Third, dexrazoxane increased cell viability and protect heart function by decreasing both cardiomyocyte apoptosis and necroptosis after doxorubicin treatment. Forth, dexrazoxane attenuated doxorubicin-induced inflammation and necroptosis by the inhibition of p38MAPK/NF-κB pathways. These results indicated that dexrazoxane ameliorates cardiotoxicity and protects heart function by attenuating both apoptosis and necroptosis in doxorubicin induced cardiomyocyte injury.

Reductive Coupling between C-N and C-O Electrophiles.

The cross-electrophile reaction is a promising strategy for C-C bond formation. Recent studies have focused mainly on reactions with organic halides. Here we report a coupling reaction between C-N and C-O electrophiles that demonstrates the possibility of constructing a C-C bond via C-N and C-O cleavage. Several reactions between benzyl/aryl ammonium salts and vinyl/aryl C-O electrophiles have been studied. Preliminary mechanistic studies revealed that the benzyl ammoniums were activated through a radical mechanism.

Aß1-42 Oligomers Induced a Short-Term Increase of Glutamate Release Prior to Its Depletion As Measured by Amperometry on Single Varicosities.

Glutamate (Glu) is a critical neurotransmitter for neuronal communication in the nervous system. In vivo studies have shown that the concentration of Glu is reduced within the brains of those afflicted with Alzheimer's disease (AD), which is also associated with the accumulation of pathogenic amyloid-beta (Aß). However, the effects of Aß peptides on the level of Glu release, as well as how Aß-mediated Glu fluctuation is initiated, remain largely unknown. Here, we fabricated a Glu electrochemical biosensor and in situ quantitatively monitored the release of Glu from a single varicosity of Aß1-42-insulted hippocampal neurons. We found that before the depletion of Glu after 300 min of treatment with Aß1-42, a short-duration (30 min) incubation with Aß1-42 caused a dramatic increase in vesicular Glu release compared to that of a control. Further investigation demonstrated that the density of vesicular glutamate transporter 1 (VGLUT1), which is responsible for transport of Glu into synaptic vesicles, also displayed a significant elevation and then dramatic depletion with the extension of the time of treatment with Aß1-42. These results indicate that at the early stage of AD, Aß1-42 induces excessive Glu release, which may overstimulate the N-methyl-d-aspartic acid (NMDA) receptor, resulting in excitotoxicity and damage to neurons. In this work, the amount of Glu released together with its fluctuations under Aß1-42 oligomers toxicity conditions was monitored for the first time, and such monitoring could provide direct and new insights for current research on Aß1-42-induced abnormalities in neurotransmitter release and neuron functions.

K+ Efflux Antiporters 4, 5, and 6 Mediate pH and K+ Homeostasis in Endomembrane Compartments.

KEA4, KEA5, and KEA6 are members of the Arabidopsis (Arabidopsis thaliana) K+ efflux antiporter (KEA) family that share high sequence similarity but whose function remains unknown. Here, we show their gene expression pattern, subcellular localization, and physiological function in Arabidopsis. KEA4, KEA5, and KEA6 had similar tissue expression patterns, and the three KEA proteins localized to the Golgi, the trans-Golgi network, and the prevacuolar compartment/multivesicular bodies, suggesting overlapping roles of these proteins in the endomembrane system. Phenotypic analyses of single, double, and triple mutants confirmed functional redundancy. The triple mutant kea4 kea5 kea6 had small rosettes, short seedlings, and was sensitive to low K+ availability and to the sodicity imposed by high salinity. Also, the kea4 kea5 kea6 mutant plants had a reduced luminal pH in the Golgi, trans-Golgi network, prevacuolar compartment, and vacuole, in accordance with the K/H exchange activity of KEA proteins. Genetic analysis indicated that KEA4, KEA5, and KEA6 as well as endosomal Na+/H+exchanger5 (NHX5) and NHX6 acted coordinately to facilitate endosomal pH homeostasis and salt tolerance. Neither cancelling nor overexpressing the vacuolar antiporters NHX1 and NHX2 in the kea4 kea5 kea6 mutant background altered the salt-sensitive phenotype. The NHX1 and NHX2 proteins in the kea4 kea5 kea6 mutant background could not suppress the acidity of the endomembrane system but brought the vacuolar pH close to wild-type values. Together, these data signify that KEA4, KEA5, and KEA6 are endosomal K+ transporters functioning in maintaining pH and ion homeostasis in the endomembrane network.

Prevalence and genotype distribution of human papillomavirus among 9945 women from the Nanhai area of Foshan.

BACKGROUND: To provide a scientific basis for the prevention and treatment of cervical cancer (CC), we investigated the distribution characteristics and genotypes of human papillomavirus (HPV) and the prevalence of multiple HPV infections in women of different ages seeking management for abnormal cytology in Foshan City. METHODS: Screening for the 21 genotypes of HPV was carried out in 9945 females seeking management of abnormal cervical cytology results using rapid flow-through hybridization of nucleic acid molecules. The overall prevalence, genotype distribution and age-specific prevalence were examined. RESULTS: Our results indicate that the prevalence of overall, high-risk, intermediate-risk, and low-risk HPV infections was 13.5%, 12.1%, 1.3%, and 1.9%, respectively. Of the 1346 women who tested positive, 89.5% were positive for a single HPV genotype, and 10.5% were positive for ≥2 genotypes. The most frequently detected HPV genotype was HPV-16 (2.9%), followed by HPV-52 (2.9%), HPV-58 (1.5%), and HPV-CP8304 (1.0%). The highest infection prevalence was found in patients 21-30 years old (271/1670, 16.2%). CONCLUSION: The prevalence of HPV infection in women seeking management for abnormal cytology in Foshan City is highest in the younger population (21-30 years old). Similar to most previous surveys, HPV-58 and HPV-52 infections are as common as HPV-16 infection.

Electrochemical Monitoring of ROS/RNS Homeostasis Within Individual Phagolysosomes Inside Single Macrophages.

The existence of a homeostatic mechanism regulating reactive oxygen/nitrogen species (ROS/RNS) amounts inside phagolysosomes has been invoked to account for the efficiency of this process but could not be unambiguously documented. Now, intracellular electrochemical analysis with platinized nanowire electrodes (Pt-NWEs) allowed monitoring ROS/RNS effluxes with sub-millisecond resolution from individual phagolysosomes impacting onto the electrode inserted inside a living macrophage. This shows for the first time that the consumption of ROS/RNS by their oxidation at the nanoelectrode surface stimulates the production of significant ROS/RNS amounts inside phagolysosomes. These results establish the existence of the long-postulated ROS/RNS homeostasis and allows its kinetics and efficiency to be quantified. ROS/RNS concentrations may then be maintained at sufficiently high levels for sustaining proper pathogen digestion rates without endangering the macrophage internal structures.

Flexible Electrochemical Urea Sensor Based on Surface Molecularly Imprinted Nanotubes for Detection of Human Sweat.

Flexible electrochemical (EC) sensors have shown great prospect in epidermal detection for personal healthcare and disease diagnosis. However, no reports have been seen in flexible device for urea analysis in body fluids. Herein, we developed a flexible wearable EC sensor based on surface molecularly imprinted nanotubes for noninvasive urea monitoring with high selectivity in human sweat. The flexible EC sensor was prepared by electropolymerization of 3,4-ethylenedioxythiophene (EDOT) monomer on the hierarchical network of carbon nanotubes (CNTs) and gold nanotubes (Au NTs) to imprint template molecule urea. This sensor exhibited a good linear response toward physiologically relevant urea levels with negligible interferences from common coexisting species. Bending test revealed that this sensor possessed excellent mechanical tolerance and its EC performance was almost not affected by bending deformation. On-body results of human subjects showed that the flexible platform could distinctly respond to the urea levels in volunteer's sweat after aerobic exercise. The new flexible epidermal EC sensor can provide useful insights into noninvasive monitoring of urea levels in various biofluids, which is promising in the clinical diagnosis of diverse biomedical applications.

Na+ ,K+ /H+ antiporters regulate the pH of endoplasmic reticulum and auxin-mediated development.

AtNHX5 and AtNHX6 are endosomal Na+ ,K+ /H+ antiporters that are critical for growth and development in Arabidopsis, but the mechanism behind their action remains unknown. Here, we report that AtNHX5 and AtNHX6, functioning as H+ leak, control auxin homeostasis and auxin-mediated development. We found that nhx5 nhx6 exhibited growth variations of auxin-related defects. We further showed that nhx5 nhx6 was affected in auxin homeostasis. Genetic analysis showed that AtNHX5 and AtNHX6 were required for the function of the endoplasmic reticulum (ER)-localized auxin transporter PIN5. Although AtNHX5 and AtNHX6 were colocalized with PIN5 at ER, they did not interact directly. Instead, the conserved acidic residues in AtNHX5 and AtNHX6, which are essential for exchange activity, were required for PIN5 function. AtNHX5 and AtNHX6 regulated the pH in ER. Overall, AtNHX5 and AtNHX6 may regulate auxin transport across the ER via the pH gradient created by their transport activity. H+ -leak pathway provides a fine-tuning mechanism that controls cellular auxin fluxes.

Toll-like receptor-mediated IRE1α activation as a therapeutic target for inflammatory arthritis.

In rheumatoid arthritis (RA), macrophage is one of the major sources of inflammatory mediators. Macrophages produce inflammatory cytokines through toll-like receptor (TLR)-mediated signalling during RA. Herein, we studied macrophages from the synovial fluid of RA patients and observed a significant increase in activation of inositol-requiring enzyme 1α (IRE1α), a primary unfolded protein response (UPR) transducer. Myeloid-specific deletion of the IRE1α gene protected mice from inflammatory arthritis, and treatment with the IRE1α-specific inhibitor 4U8C attenuated joint inflammation in mice. IRE1α was required for optimal production of pro-inflammatory cytokines as evidenced by impaired TLR-induced cytokine production in IRE1α-null macrophages and neutrophils. Further analyses demonstrated that tumour necrosis factor (TNF) receptor-associated factor 6 (TRAF6) plays a key role in TLR-mediated IRE1α activation by catalysing IRE1α ubiquitination and blocking the recruitment of protein phosphatase 2A (PP2A), a phosphatase that inhibits IRE1α phosphorylation. In summary, we discovered a novel regulatory axis through TRAF6-mediated IRE1α ubiquitination in regulating TLR-induced IRE1α activation in pro-inflammatory cytokine production, and demonstrated that IRE1α is a potential therapeutic target for inflammatory arthritis.

Deleted in Breast Cancer 1 Suppresses B Cell Activation through RelB and Is Regulated by IKKα Phosphorylation.

Alternative NF-κB signaling is crucial for B cell activation and Ig production, and it is mainly regulated by the inhibitor of κ B kinase (IKK) regulatory complex. Dysregulation of alternative NF-κB signaling in B cells could therefore lead to hyperactive B cells and Ig overproduction. In our previous, study we found that deleted in breast cancer 1 (DBC1) is a suppressor of the alternative NF-κB pathway to attenuate B cell activation. In this study, we report that loss of DBC1 results in spontaneous overproduction of Ig in mice after 10 mo of age. Using a double mutant genetic model, we confirm that DBC1 suppresses B cell activation through RelB inhibition. At the molecular level, we show that DBC1 interacts with alternative NF-κB members RelB and p52 through its leucine zipper domain. In addition, phosphorylation of DBC1 at its C terminus by IKKα facilitates its interaction with RelB and IKKα, indicating that DBC1-mediated suppression of alternative NF-κB is regulated by IKKα. Our results define the molecular mechanism of DBC1 inhibition of alternative NF-κB activation in suppressing B cell activation.

Real-Time Intracellular Measurements of ROS and RNS in Living Cells with Single Core-Shell Nanowire Electrodes.

Nanoelectrodes allow precise and quantitative measurements of important biological processes at the single living-cell level in real time. Cylindrical nanowire electrodes (NWEs) required for intracellular measurements create a great challenge for achieving excellent electrochemical and mechanical performances. Herein, we present a facile and robust solution to this problem based on a unique SiC-core-shell design to produce cylindrical NWEs with superior mechanical toughness provided by the SiC nano-core and an excellent electrochemical performance provided by the ultrathin carbon shell that can be used as such or platinized. The use of such NWEs for biological applications is illustrated by the first quantitative measurements of ROS/RNS in individual phagolysosomes of living macrophages. As the shell material can be varied to meet any specific detection purpose, this work opens up new opportunities to monitor quantitatively biological functions occurring inside cells and their organelles.

DBC1 is a suppressor of B cell activation by negatively regulating alternative NF-κB transcriptional activity.

CD40 and BAFFR signaling play important roles in B cell proliferation and Ig production. In this study, we found that B cells from mice with deletion of Dbc1 gene (Dbc1(-/-)) show elevated proliferation, and IgG1 and IgA production upon in vitro CD40 and BAFF, but not BCR and LPS stimulation, indicating that DBC1 inhibits CD40/BAFF-mediated B cell activation in a cell-intrinsic manner. Microarray analysis and chromatin immunoprecipitation experiments reveal that DBC1 inhibits B cell function by selectively suppressing the transcriptional activity of alternative NF-κB members RelB and p52 upon CD40 stimulation. As a result, when immunized with nitrophenylated-keyhole limpet hemocyanin, Dbc1(-/-) mice produce significantly increased levels of germinal center B cells, plasma cells, and Ag-specific Ig. Finally, loss of DBC1 in mice leads to higher susceptibility to experimental autoimmune myasthenia gravis. Our study identifies DBC1 as a novel regulator of B cell activation by suppressing the alternative NF-κB pathway.