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Four new species, Xynobius azonius sp. nov., X. brevifemora sp. nov., X. duoferus sp. nov., and X. stipitoides sp. nov., are described and illustrated, and one species X. geniculatus (Thomson, 1895) is newly reported from South Korea. Xynobius geniculatus (Thomson, 1895) is redescribed and illustrated, and a new combination, Xynobius (Stigmatopoea) cubitalis (Fischer, 1959), comb. nov. is suggested. An identification key to the Xynobius species known from South Korea is provided.

Pleosporales comprise a diverse group of fungi with a global distribution and significant ecological importance. A survey on Pleosporales (in Didymosphaeriaceae, Roussoellaceae and Nigrogranaceae) in Guizhou Province, China, was conducted. Specimens were identified, based on morphological characteristics and phylogenetic analyses using a dataset composed of ITS, LSU, SSU, tef1 and rpb2 loci. Maximum Likelihood (ML) and Bayesian analyses were performed. As a result, three new species (Neokalmusia karka, Nigrograna schinifolium and N. trachycarpus) have been discovered, along with two new records for China (Roussoella neopustulans and R. doimaesalongensis) and a known species (Roussoella pseudohysterioides). Morphologically similar species and phylogenetically close taxa are compared and discussed. This study provides detailed information and descriptions of all newly-identified taxa.

Manganese (Mn) pollution poses a serious threat to the health of animals, plants, and humans. The microbial-mediated Mn(II) removal method has received widespread attention because of its rapid growth, high efficiency, and economy. Mn(II)-oxidizing bacteria can oxidize toxic soluble Mn(II) into non-toxic Mn(III/IV) oxides, which can further participate in the transformation of other heavy metals and organic pollutants, playing a crucial role in environmental remediation. This study aims to conduct a bibliometric analysis of research papers on bacterial Mn(II) oxidation using CiteSpace, and to explore the research hotspots and developmental trends within this field between 2008 and 2023. A series of visualized knowledge map analyses were conducted with 469 screened SCI research papers regarding annual publication quantity, author groups and their countries and regions, journal categories, publishing institutions, and keywords. China, the USA, and Japan published the most significant number of research papers on the research of bacterial Mn(II) oxidation. Research hotspots of bacterial Mn(II) oxidation mainly focused on the species and distributions of Mn(II)-oxidizing bacteria, the influencing factors of Mn(II) oxidation, the mechanisms of Mn(II) oxidation, and their applications in environment. This bibliometric analysis provides a comprehensive visualized knowledge map to quickly understand the current advancements, research hotspots, and academic frontiers in bacterial Mn(II) oxidation.

The population of Caragana tibetica, situated on the edge of the typical grassland-to-desert transition in the Mu Us Sandy Land, plays a vital ecological role in maintaining stability within the regional fragile ecosystem. Despite the consistent growth of C. tibetica following animal grazing, the biological mechanisms underlying its compensatory growth in response to livestock consumption remain unclear. Analyzing 48 metabolomic profiles from C. tibetica, our study reveals that the grazing process induces significant changes in the metabolic pathways of C. tibetica branches. Differential metabolites show correlations with soluble protein content, catalase, peroxidase, superoxide dismutase, malondialdehyde, and proline levels. Moreover, machine learning models built on these differential metabolites accurately predict the intensity of C. tibetica grazing (with an accuracy of 83.3%). The content of various metabolites, indicative of plant stress responses, including Enterolactone, Narceine, and Folcepri, exhibits significant variations in response to varying grazing intensities (P

IntroductionThe biosynthesis of the secondary cell wall (SCW) is orchestrated by an intricate hierarchical transcriptional regulatory network. This network is initiated by first-layer master switches, SCW-NAC transcription factors, which in turn activate the second-layer master switches MYBs. These switches play a crucial role in regulating xylem specification and differentiation during SCW formation. However, the roles of most MYBs in woody plants are yet to be fully understood.MethodsIn this study, we identified and isolated the R2R3-MYB transcription factor, PtoMYB031, from Populus tomentosa. We explored its expression, mainly in xylem tissues, and its role as a transcriptional repressor in the nucleus. We used overexpression and RNA interference techniques in poplar, along with Yeast two-hybrid (Y2H) and bimolecular fluorescence complementation (BiFC) assays, to analyze the regulatory effects of PtoMYB031.ResultsOverexpression of PtoMYB031 in poplar significantly reduced lignin, cellulose, and hemicellulose content, and inhibited vascular development in stems, resulting in decreased SCW thickness in xylem tissues. Gene expression analysis showed that structural genes involved in SCW biosynthesis were downregulated in PtoMYB031-OE lines. Conversely, RNA interference of PtoMYB031 increased these compounds. Additionally, PtoMYB031 was found to recruit the repressor PtoZAT11, forming a transcriptional inhibition complex.DiscussionOur findings provide new insights into how PtoMYB031, through its interaction with PtoZAT11, forms a complex that can suppress the expression of key regulatory genes, PtoWND1A and PtoWND2B, in SCW biosynthesis. This study enhances our understanding of the transcriptional regulation involved in SCW formation in poplar, highlighting the significant role of PtoMYB031.

The lakes of Jianghan Plain, as an important component of the water bodies in the middle and lower reaches of the Yangtze River plain, have made significant contributions to maintaining the ecological health and promoting the sustainable development of the Jianghan Plain. However, there is a relatively limited understanding regarding the trends of lake area change for different types of lakes and their dominant factors over the past three decades in the Jianghan Plain. Based on the Google Earth Engine (GEE) platform, combined with the water body index method, the changes in area of three different types of lakes (area > 1 km2) in the Jianghan Lake Group from 1990 to 2020 were extracted and analyzed. Additionally, the Partial least squares structural equation model (PLS-SEM) was utilized to analyze the driving factors affecting the changes in water body area of these lakes. The results show that from 1990 to 2020, the area of the lakes of the wet season and level season exhibited a decreasing trend, decreasing by 893.1 km2 and 77.9 km2, respectively. However, the area of dry season lakes increased by 59.27 km2. The areas of all three types of lakes reached their minimum values in 2006. According to the PLS-SEM results, the continuous changes in the lakes’ area are mainly controlled by environmental factors overall. Furthermore, human factors mainly influence the mutation of the lakes’ area. This study achieved precise extraction of water body areas and accurate analysis of driving factors, providing a basis for a comprehensive understanding of the dynamic changes in the lakes of Jianghan Plain, which is beneficial for the rational utilization and protection of water resources.

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During the research on rust fungi in medicinal plants of Guizhou Province, China, a total of 9 rust fungal species were introduced, including 3 new species (Hamaspora rubi-alceifolii, Nyssopsora altissima, and Phragmidium cymosum), as well as 6 known species (Melampsora laricis-populina, Melampsoridium carpini, Neophysopella ampelopsidis, Nyssopsora koelrezidis, P. rosae-roxburghii, P. tormentillae). Notably, N. ampelopsidis and P. tormentillae were discovered for the first time in China, while M. laricis-populina, Me. carpini, and Ny. koelreuteriae were first documented in Guizhou Province. Morphological observation and molecular phylogenetic analyses of these species with similar taxa were compared to confirm their taxonomic identities, and taxonomic descriptions, illustrations and host species of those rust fungi on medicinal plant are provided.

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths worldwide. Emerging therapies, such as ferroptosis mediated cancer therapy and phototherapy, offer new opportunities for HCC treatment. The combination of multiple treatments is often more effective than monotherapy, but many of the current treatments are prone to serious side effects, resulting in a serious decline in patients’ quality of life. Therefore, the combination therapy of tumor in situ controllable activation will improve the efficacy and reduce side effects for precise treatment of tumor. Herein, we synthesized a GSH-activatable nanomedicine to synergize photothermal therapy (PTT) and ferrotherapy. We utilized a near-infrared dye SQ890 as both an iron-chelating and a photothermal converter agent, which was encapsulated with a GSH-sensitive polymer (PLGA-SS-mPEG), to attain the biocompatible SQ890@Fe nanoparticles (NPs). In the tumor microenvironment (TME), SQ890@Fe NPs showed a GSH-activated photothermal effect that could increase the Fenton reaction rate. Meanwhile, the depletion of GSH could further increase ferroptosis effect. In turn, the increasing radical generated by ferrotherapy could impair the formation of heat shock proteins (HSPs) which could amplify PTT effects by limiting the self-protection mechanism. Overall, the intelligent nanomedicine SQ890@Fe NPs combines ferrotherapy and PTT to enhance the efficacy and safety of cancer treatment through the mutual promotion of the two treatment mechanisms, providing a new dimension for tumor combination therapy.

The development of B cells relies on an intricate network of transcription factors critical for developmental progression and lineage commitment. In the B cell developmental trajectory, a temporal switch from predominant Foxo3 to Foxo1 expression occurs at the CLP stage. Utilizing VAV-iCre mediated conditional deletion, we found that the loss of FOXO3 impaired B cell development from LMPP down to B cell precursors, while the loss of FOXO1 impaired B cell commitment and resulted in a complete developmental block at the CD25 negative proB cell stage. Strikingly, the combined loss of FOXO1 and FOXO3 resulted in the failure to restrict the myeloid potential of CLPs and the complete loss of the B cell lineage. This is underpinned by the failure to enforce the early B-lineage gene regulatory circuitry upon a predominantly pre-established open chromatin landscape. Altogether, this demonstrates that FOXO3 and FOXO1 cooperatively govern early lineage restriction and initiation of B-lineage commitment in CLPs.

[Objectives] This study was conducted to screen lavandulyl flavonoids with anti-inflammatory activity from Sophora flavescens. [Methods] 35 compounds were screened from traditional Chinese medicine S. flavescens using the nitric oxide (NO) anti-inflammatory activity model. [Results] Five components, 8 (xanthohumol), 13 (kurarinol), 27 (4-methoxysalicylic acid), 28 (b-resorcic acid) and 30 (b-resorcic acid), exhibited significant anti-inflammatory activity, with IC50 values of 5.99, 4.76, 6.96, 3.41 and 5.22 μM, respectively. Especially, 8 (xanthohumol) and 13 (kurarinol) were typical lavandulyl flavonoids in S. flavescens, which were worth further exploration. Furthermore, UPLC-Q-Exactive and GNPS molecular networking technique were used for rapid analysis of lavandulyl flavonoids from S. flavescens. A total of 15 components were identified. [Conclusions] This work lays a theoretical foundation for further separation and analysis of lavandulyl flavonoids with anti-inflammatory activity from S. flavescens. [ABSTRACT FROM AUTHOR]

Both lncRNAs and the N6-methyladenosine (m6A) modification are key regulators of tumorigenesis and innate immunity. However, little is known about the m6A modification of lncRNAs and their clinical and immune relevance in bladder cancer. In this study, we identified m6A-related lncRNAs using Pearson correlation analysis in The Cancer Genome Atlas (TCGA) and the IMvigor210 datasets. Next, univariate Cox regression was performed using the TCGA dataset to filter prognostic m6A-related lncRNAs, which were further subjected to the least absolute shrinkage and selection operator (LASSO) Cox regression to establish a 12 m6A-related lncRNA prognostic score (m6A-LRS). The m6A-LRS was validated in the IMvigor210 dataset. In addition, high m6A-LRS tumors, characterized by decreased tumor mutation load and neoantigen load, showed poorer response to immunotherapy than those with low m6A-LRS in the IMvigor210 dataset. Further, we constructed an m6A-LRS-based nomogram that demonstrated a strong ability to predict overall survival in patients with bladder cancer. Moreover, enrichment analysis revealed that tumor-associated biological processes, oncogenic signaling, and tumor hallmarks were commonly associated with a high m6A-LRS. Gene set variation analysis also indicated that high m6A-LRS was associated with activation of canonical oncogenic signatures, such as the epithelial-to-mesenchymal transition, cell cycle regulators, and DNA replication, as well as activation of immunosuppressive signatures, such as the T-cell exhaustion and pan-fibroblast-TGF-β response signatures. Furthermore, we observed distinct tumor microenvironment cell infiltration characteristics between high- and low-risk tumors. High m6A-LRS tumors showed reduced infiltration of CD8+ T-cells and enhanced infiltration of macrophages and fibroblasts. Additionally, we established a competing endogenous RNA network based on the12 m6A-related lncRNAs. Finally, three lncRNAs (SNHG16, SBF2-AS1, and BDNF-AS) were selected for further validation. The qualitative PCR assay on 10 pairs of bladder cancer and adjacent normal control samples validated the differential expression, and methylated RNA immunoprecipitation (MeRIP) analysis demonstrated a robust m6A enrichment in T24 bladder cancer cells compared with normal uroepithelial cells (SVHUC-1). In conclusion, this study introduced an m6A-related lncRNA signature that identified a subgroup of patients with poor prognoses and suboptimal immune responses, thus providing novel approaches for treatment response prediction and patient stratification in bladder cancer.

[Objectives] To discover novel compounds with significant anti-inflammatory activity in the alcohol extract of Polygonum capitatum. [Methods] Firstly, a new flavonoid glycoside,capitaone B (1), was isolated from the ethyl acetate extract from P. capitatum, and then 27 compounds were screened using NO anti-inflammatory activity model. [Results] Four compounds, such as kaempferol (12), 1,2, 6-trigalloyl-β-d-glucose (15), catechin (16) and β-sitosterol (26), could significantly inhibit LPS-induced NO production in macrophages, with IC50 values of 15.31, 8.43, 6.92 and 5.72 μM, respectively. [Conclusions] The chemical composition and anti-inflammatory activity of P. capitatum were preliminarily studied, and the results provide a theoretical basis for further research on the action mechanism of subsequent anti-inflammatory active compounds of P. capitatum. [ABSTRACT FROM AUTHOR]

X-linked neutropenia (XLN) is caused by gain-of-function mutations in the actin regulator Wiskott-Aldrich Syndrome protein (WASp). XLN patients have reduced numbers of cytotoxic cells in peripheral blood; however, their capacity to kill tumor cells remains to be determined. Here, we examined NK and T cells from 2 patients with XLN harboring the activating WASpL270P mutation. XLN patient NK and T cells had increased granzyme B content and elevated degranulation and IFN-γ production when compared with healthy control cells. Murine WASpL272P NK and T cells formed stable synapses with YAC-1 tumor cells and anti-CD3/CD28–coated beads, respectively. WASpL272P mouse T cells had normal degranulation and cytokine response whereas WASpL272P NK cells showed an enhanced response. Imaging experiments revealed that while WASpL272P CD8+ T cells had increased accumulation of actin upon TCR activation, WASpL272P NK cells had normal actin accumulation at lytic synapses triggered through NKp46 signaling but had impaired response to lymphocyte function associated antigen-1 engagement. When compared with WT mice, WASpL272P mice showed reduced growth of B16 melanoma and increased capacity to reject MHC class I–deficient cells. Together, our data suggest that cytotoxic cells with constitutively active WASp have an increased capacity to respond to and kill tumor cells.

Megakaryoblastic leukemia 1 (MKL1) is a coactivator of serum response factor and together they regulate transcription of actin cytoskeleton genes. MKL1 is associated with hematologic malignancies and immunodeficiency, but its role in B cells is unexplored. Here we examined B cells from monozygotic triplets with an intronic deletion in MKL1, two of whom had been previously treated for Hodgkin lymphoma (HL). To investigate MKL1 and B-cell responses in the pathogenesis of HL, we generated Epstein-Barr virus-transformed lymphoblastoid cell lines from the triplets and two controls. While cells from the patients with treated HL had a phenotype close to that of the healthy controls, cells from the undiagnosed triplet had increased MKL1 mRNA, increased MKL1 protein, and elevated expression of MKL1-dependent genes. This profile was associated with elevated actin content, increased cell spreading, decreased expression of CD11a integrin molecules, and delayed aggregation. Moreover, cells from the undiagnosed triplet proliferated faster, displayed a higher proportion of cells with hyperploidy, and formed large tumors in vivo. This phenotype was reversible by inhibiting MKL1 activity. Interestingly, cells from the triplet treated for HL in 1985 contained two subpopulations: one with high expression of CD11a that behaved like control cells and the other with low expression of CD11a that formed large tumors in vivo similar to cells from the undiagnosed triplet. This implies that pre-malignant cells had re-emerged a long time after treatment. Together, these data suggest that dysregulated MKL1 activity participates in B-cell transformation and the pathogenesis of HL.

Objectives] To explore the pharmacodynamic material basis of Sijicao granules for the treatment of eczema through chemical com- position-network pharmacology. [Methods] First of all, the chemical constituents of Polygonum capitatum and Plantago asiatica from Sijicao granules were collected, and the relevant target information of the constituents was collected by TCMSP, PubChem, DisGeNET, GeneCards and STRING databases. Furthermore, Cytoscape 3.8.2 software was used to construct the chemical compounds-target network map of Sijicao granules. Finally, STRING database was used for PPI protein network analysis, GO functional enrichment analysis and KEGG pathway enrich- ment analysis of core targets, and molecular docking between core constituents and protein targets was also performed. [Results] 30 constitu- ents, including quercetin, kaempferol, luteolin, ellagic acid and gallic acid, were discovered to be the key effective compounds of Sijicao gran- ules in the treatment of eczema. And its core action protein targets were PTGS2, NOS2, AKTI, TP53, IL6, HMOX1. What's more, through GO functional enrichment analysis of biological process (BP), cell component (CC), molecular function (MF) analysis and KEGG pathway enrichment analysis, the main pathways of action of Sijicao granules for the treatment of eczema including IL-17 signaling pathway, T cell re- ceptor signaling pathway, cancer signaling pathway, TNF signaling pathway and Relaxin signaling pathway. In addition, molecular docking re- sults displayed that the primary active constituents quercetin, kaempferol and luteolin were well combined with the core protein targets AKTI and IL6. [Conclusions] Sijicao granules could play an important role for the treatment of eczema through multi-component, multi-target, multi-pathway and their interaction. [ABSTRACT FROM AUTHOR]

The germinal center (GC) is a transient anatomical structure formed during the adaptive immune response that leads to antibody affinity maturation and serological memory. Recent works using two-photon microscopy reveals that the GC is a highly dynamic structure and GC B cells are highly motile. An efficient selection of high affinity B cells clones within the GC crucially relies on the interplay of proliferation, genome editing, cell-cell interaction, and migration. All these processes require actin cytoskeleton rearrangement to be well-coordinated. Dysregulated actin dynamics may impede on multiple stages during B cell affinity maturation, which could lead to aberrant GC response and result in autoimmunity and B cell malignancy. This review mainly focuses on the recent works that investigate the role of actin regulators during the GC response.

Heterochromatin Protein 1 (HP1) is a conserved chromosomal protein in eukaryotic cells that has a major role in directing heterochromatin formation, a process that requires co-transcriptional gene silencing mediated by small RNAs and their associated argonaute proteins. Heterochromatin formation requires erasing the active epigenetic mark, such as H3K4me2, but the molecular link between HP1 and H3K4 demethylation remains unclear. In a fertility screen in female Drosophila, we identified ovaries absent (ova), which functions in the stem cell niche, downstream of Piwi, to support germline stem cell differentiation. Moreover, ova acts as a suppressor of position effect variegation, and is required for silencing telomeric transposons in the germline. Biochemically, Ova acts to link the H3K4 demethylase dLsd1 to HP1a for local histone modifications. Therefore, our study provides a molecular connection between HP1a and local H3K4 demethylation during HP1a-mediated gene silencing that is required for ovary development, transposon silencing, and heterochromatin formation.Editorial note: This article has been through an editorial process in which the authors decide how to respond to the issues raised during peer review. The Reviewing Editor's assessment is that all the issues have been addressed (see decision letter).

To investigate the systematic evaluation of pharmacognostic identification of Polygonum capitatum. [Methods] 10 batches of P. capitatum cultivated in Guizhou were chosen for plant samples. Macroscopical identification was conducted on plant roots, stems, leaves, flowers and fruits. The P. capitatum powder was processed for physical and chemical distinction by FeCl3 chromogenic reaction, hydrochloric acid magnesium powder reaction, A1C13 color development reaction and thin-layer chromatography. Microscope identification was carried out on the powder. Plant genome DNeasy Plant Kit was adopted for DNA molecular marker identification. [Results] The results showed that the stem of P. capitatum was tufted, the leaves were oval, 2 to 5 cm long, and 1 to 2 cm wide; the leaf apex was acute and cuneate at the base, the inflorescence was capitate, paired or solitary; the raceme was erect and nearly spherical, and the perianth was light red. Furthermore, for the chromogenic reaction of FeCl3 ethanol extract of P. capitatum, appeared blue and turned to dark blue after long time storing at room temperature. For the reaction of hydrochloric acid magnesium powder, the alcohol extract of P. capitatum, exhibited deep red. In the color reaction of A1C1, the alcohol extract revealed yellow fluorescence under 360 nm UV lamp. Microscope identification of the powder displayed pollen grains, crystal sheath fibers, cellulose, vessels, starch grains, cork cells, and other characteristic fragments. In addition, DNA barcoding electrophoresis results showed that P. capitatum showed a clear and bright single band near 500 bp, and further sequencing results showed that the sequence differences were mainly concentrated in 1TS1 and 1TS2 region. [Conclusions] Systematic evaluation for the identification of P. capitatum is established, which combines with macroscopic identification, physicochemical identification, powder microscope identification, and DNA molecular identification. Finally, the original medicinal material is identified as P. capitatum Buch. -Ham. ex D. Don. [ABSTRACT FROM AUTHOR]

This genome-wide association study on persistent hepatitis B virus (HBV) infection among Chinese confirms previously associated genetic loci while discovering a novel protective locus at 8p21.3. The study also demonstrates the nearby gene INST10 suppresses HBV replication in vitro.

The Wiskott-Aldrich syndrome protein (WASp) is a key regulator of the actin cytoskeleton in hematopoietic cells and mutated in two severe immunodeficiency diseases with high incidence of cancer. Wiskott-Aldrich syndrome (WAS) is caused by loss-of-function mutations in WASp and most frequently associated with lymphoreticular tumors of poor prognosis. X-linked neuropenia (XLN) is caused by gain-of-function mutations in WASp and associated with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). To understand the role of WASp in tumorigenesis, we bred WASp+, WASp−, and WASp-XLN mice onto tumor susceptible p53+/- background and sub-lethally irradiated them to enhance tumor development. We followed the cohorts for 24 weeks and tumors were characterized by histology and flow cytometry to define the tumor incidence, onset, and cell origin. We found that p53+/-WASp+ mice developed malignancies, including solid tumors and T cell lymphomas with 71.4% of survival 24 weeks after irradiation. p53+/-WASp− mice showed lower survival rate and developed various early onset malignancies. Surprisingly, the p53+/-WASp-XLN mice developed malignancy mostly with late onset, which caused delayed mortality in this colony. This study provides evidence for that loss-of-function and gain-of-function mutations in WASp influence tumor incidence and onset.

The Rho GTPases Cdc42, Rac1, and Rac2 coordinate receptor signaling to cell adhesion, migration, and proliferation. Deletion of Rac1 and Rac2 early during B cell development leads to failure in B cell entry into the splenic white pulp. Here, we sought to understand the role of Rac1 and Rac2 in B cell functionality and during the humoral antibody response. To circumvent the migratory deficiency of B cells lacking both Rac1 and Rac2, we took the approach to inducibly delete Rac1 in Rac2−/− B cells in the spleen (Rac1BRac2−/− B cells). Rac1BRac2−/− mice had normal differentiation of splenic B cell populations, except for a reduction in marginal zone B cells. Rac1BRac2−/− B cells showed normal spreading response on antibody-coated layers, while both Rac2−/− and Rac1BRac2−/− B cells had reduced homotypic adhesion and decreased proliferative response when compared to wild-type B cells. Upon challenge with the T-cell-independent antigen TNP-conjugated lipopolysaccharide, Rac1BRac2−/− mice showed reduced antibody response. In contrast, in response to the T-cell-dependent antigen sheep red blood cells, Rac1BRac2−/− mice had increased serum titers of IgG1 and IgG2b. During in vitro Ig class switching, Rac1BRac2−/− B cells had elevated germline γ2b transcripts leading to increased Ig class switching to IgG2b. Our data suggest that Rac1 and Rac2 serve an important role in regulation of the B cell humoral immune response and in suppressing Ig class switching to IgG2b.

We sought to identify genes necessary to induce cytoskeletal change in B cells. Using gene expression microarray, we compared B cells stimulated with interleukin-4 (IL-4) and anti-CD40 antibodies that induce B cell spreading, cell motility, tight aggregates, and extensive microvilli with B cells stimulated with lipopolysaccharide that lack these cytoskeletal changes. We identified 84 genes with 10-fold or greater expression in anti-CD40 + IL-4 stimulated B cells, one of these encoded the guanine nucleotide exchange factor (GEF) dedicator of cytokinesis 10 (Dock10). IL-4 selectively induced Dock10 expression in B cells. Using lacZ expression to monitor Dock10 promoter activity, we found that Dock10 was expressed at all stages during B cell development. However, specific deletion of Dock10 in B cells was associated with a mild phenotype with normal B cell development and normal B cell spreading, polarization, motility, chemotaxis, aggregation, and Ig class switching. Dock10-deficient B cells showed lower proliferation in response to anti-CD40 and IL-4 stimulation. Moreover, the IgG response to soluble antigen in vivo was lower when Dock10 was specifically deleted in B cells. Together, we found that most B cell responses were intact in the absence of Dock10. However, specific deletion of Dock10 in B cells was associated with a mild reduction in B cell activation in vitro and in vivo.