Germinal center (GC) response ensures the generation of diverse and high-affinity antibodies during the T cell-dependent (TD) immune response. This process is controlled by coordinated transcriptional and posttranscriptional gene regulatory mechanisms. Minor intron splicing is known to be involved in posttranscriptional regulation of gene expression. RNA-binding region (RNP1, RRM) containing 3 (RNPC3) is a minor spliceosome component involved in stabilizing the U11/U12 di-snRNP complex, which is essential for minor intron splicing. However, it remains unclear if RNPC3 and RNPC3-related gene regulatory mechanisms are important for the TD immune response. In this study, we conditionally ablated RNPC3 in activated B cells and showed that the mutant mice had defective antibody generation due to impaired GC B cell response. We demonstrate that RNPC3 deficiency inhibits the proliferation and promotes the apoptosis of activated B cells. Mechanistically, we show that RNPC3 regulates the development of GC B cells in a minor spliceosome-dependent manner by controlling the removal of minor introns from minor intron-containing genes associated with cell proliferation and apoptosis. Our study thus uncovers a previously unappreciated role for RNPC3 in regulating GC B cell response.
© 2025 Wiley‐VCH GmbH.

Myricetin is a bioactive compound in many edible plants. We have previously demonstrated that myricetin could significantly protect mice against colitis by regulating Treg/Th17 balance, while underlying mechanism remains unclear. The current study aimed to unravel the potential regulating mechanism of myricetin.
The concentrations of 22 amino acids in colon were determined using HPLC-MS/MS and principal component analysis (PCA) was performed on the data. MetaboAnalyst was used to detect potential biological pathway influenced by myricetin. The results were further verified using qPCR, molecular docking method, and AhR inhibitor.
Studies had found that the biosynthesis of phenylalanine, tyrosine, and tryptophan; phenylalanine metabolism; and histidine metabolism were the most important pathways related to myricetin. Therefore, the aryl hydrocarbon receptor (AhR), which is closely related to the metabolism of tryptophan, phenylalanine, and tyrosine, was postulated to be the underlying signaling pathways. Furthermore, administration of myricet in significantly increased the relative expressions of CYP1A1 and CYP1B1, whereas AhR inhibitor abolished the amelioration of myricetin on DSS-induced colitis. Moreover, AhR inhibitor weakened the regulatory effect of myricetin on Treg/Th17 balance. Furthermore, the results obtained by the molecular docking method speculated that myricetin could bind to AhR as a ligand and activate AhR.
The results suggested that myricetin could exert its protection against dextran sulfate sodium (DSS)-induced colitis by activating AhR signaling pathway.
© 2025 Tao Xu et al.

The bone marrow (BM) niche is critical in regulating hematopoiesis, and sexual dimorphism and its underlying mechanism in the BM niche and its impact on hematopoiesis are not well understood. We show that male mice exhibited a higher abundance of leptin-receptor-expressing mesenchymal stromal cells (LepR-MSCs) compared with female mice. Sex-mismatched coculture and BM transplantation showed that the male BM niche provided superior support for in vitro colony formation and in vivo hematopoietic engraftment. The cotransplantation of male stromal cells significantly enhanced engraftment in female recipients. Single-cell RNA-seq revealed that the lower expression of the X-linked lysine H3K4 demethylase, Kdm5c, in male MSCs led to the increased expression of Cxcl12. In MSC-specific Kdm5c-KO mouse model, the reduction of KDM5C in female MSCs enhanced MSC quantity and function, ultimately improving engraftment to the male level. Kdm5c thus plays a role in driving sexual dimorphism in the BM niche and hematopoietic regeneration. Our study unveils a sex-dependent mechanism governing the BM niche regulation and its impact on hematopoietic engraftment. The finding offers potential implications for enhancing BM transplantation efficacy in clinical settings by harnessing the resource of male MSCs or targeting Kdm5c.

MRL/lpr mice develop systemic lupus erythematosus-like autoimmunity due to defective FAS-mediated apoptosis. We generated Fas lpr mice deficient in EAF2, a transcription elongation-associated factor known to promote apoptosis in germinal center (GC) B cells and crucial for preventing autoimmunity. Contrary to expectations, EAF2 deficiency significantly reduced lymphadenopathy and splenomegaly, extended lifespan, and alleviated nephritis by decreasing renal immune complex deposition. Additionally, EAF2 deficiency markedly reduced accumulation of activated B cells, GC B cells, plasma cells, and the abnormal B220+CD3+ T cells in Fas lpr mice. Further analysis revealed that Eaf2 -/- Fas lpr B cells showed hyperactivation upon various stimulations, followed by increased death. RNA sequencing of the B220+CD3+ cells revealed a downregulation in survival-promoting genes such as Bcl-2 and Akt and an upregulation of proapoptotic genes. We conclude that the combined deficiency in FAS- and EAF2-mediated apoptotic pathways leads to B cell hyperactivation and subsequent death, thereby ameliorating systemic autoimmunity in this model.
© 2024 The Author(s).

Phosphatase and tensin homolog (PTEN) is vital for B cell development, acting as a key negative regulator in the PI3K signaling pathway. We used CD23-cre to generate PTEN-conditional knockout mice (CD23-cKO) to examine the impact of PTEN mutation on peripheral B cells. Unlike mb1-cre-mediated PTEN deletion in early B cells, CD23-cKO mutants exhibited systemic inflammation with increased IL-6 production in mature B cells upon CpG stimulation. Inflammatory B cells in CD23-cKO mice showed elevated phosphatidylinositol 3-phosphate [PI(3)P] levels and increased TLR9 endosomal localization. Pharmacological inhibition of PI(3)P synthesis markedly reduced TLR9-mediated IL-6. Single-cell RNA-sequencing (RNA-seq) revealed altered endocytosis, BANK1, and NF-κB1 expression in PTEN-deficient B cells. Ectopic B cell receptor (BCR) expression on non-inflammatory mb1-cKO B cells restored BANK1 and NF-κB1 expression, enhancing TLR9-mediated IL-6 production. Our study highlights PTEN as a crucial inflammatory checkpoint, regulating TLR9/IL-6 axis by fine-tuning PI(3)P homeostasis. Additionally, BCR downregulation prevents the differentiation of inflammatory B cells in PTEN deficiency.
© 2024 The Author(s).