ENAapplication/xmlftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR106/071/SRR10673771/SRR10673771_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR106/065/SRR10673765/SRR10673765_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR106/066/SRR10673766/SRR10673766_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR106/067/SRR10673767/SRR10673767_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR106/072/SRR10673772/SRR10673772_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR106/073/SRR10673773/SRR10673773_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR106/070/SRR10673770/SRR10673770_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR106/063/SRR10673763/SRR10673763_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR106/064/SRR10673764/SRR10673764_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR106/074/SRR10673774/SRR10673774_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR106/073/SRR10673773/SRR10673773_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR106/064/SRR10673764/SRR10673764_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR106/072/SRR10673772/SRR10673772_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR106/068/SRR10673768/SRR10673768_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR106/067/SRR10673767/SRR10673767_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR106/069/SRR10673769/SRR10673769_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR106/070/SRR10673770/SRR10673770_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR106/071/SRR10673771/SRR10673771_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR106/069/SRR10673769/SRR10673769_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR106/068/SRR10673768/SRR10673768_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR106/074/SRR10673774/SRR10673774_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR106/065/SRR10673765/SRR10673765_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR106/066/SRR10673766/SRR10673766_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR106/063/SRR10673763/SRR10673763_2.fastq.gzprimaryOK200GenomicsAG Di Virgilio, Max-Delbrück-centrumhttps://www.ebi.ac.uk/ena/browser/view/PRJNA595013Mus musculusClass switch recombination (CSR) and somatic hypermutation (SHM) are antibody gene diversification reactions occurring in mature B cells that are essential for protective humoral immunity. CSR and SHM are initiated following activation by the antigen, and are dependent on efficient induction of activation-induced cytidine deaminase (AID). Therefore, mature B cell viability and fitness are crucial to mount effective immune responses. Here, we identified PDGFA-associated protein 1 (Pdap1) as an essential regulator of cellular homeostasis in mature B cells. Pdap1 deficiency leads to sustained expression of the integrated stress response (ISR) effector activating transcription factor 4 (Atf4) and induction of the ISR transcriptional program, increased cell death, and defective AID expression. As a consequence, loss of Pdap1 reduces germinal center B cell formation and impairs CSR and SHM. Thus, Pdap1 protects mature B cells against chronic ISR activation, and ensures efficient antibody diversification by promoting their survival and optimal function. Overall design: Two conditions were tested: stimulation with LPS and IL-4 (to induce CSR to IgG1) or LPS, BAFF and TGFbeta (to induce CSR to IgG2b). Samples were harvested from control and Pdap1F/FCd19Cre/+ splenocyte cultures 48 h after stimulation. Three biological replicates (= mice) per sample were employed for the analysis (control mice: C1 to C3 Pdap1F/FCd19Cre/+ mice: P1 to P3).xref:PubMed:32609329ENAfalseGene expression comparison, WT and PDAP1-deficient primary B lymphocytesGene expression comparison, WT and PDAP1-deficient primary B lymphocytes2025-09-242020-06-02PRJNA595013GSE1418761009032609329