bioRxiv : the preprint server for biology最新文献

{"title":"Cis-regulatory evolution of <i>Wnt</i>-family genes contributes to a morphological difference between silkworm species.","authors":"Kenta Tomihara, Ana Pinharanda, Young Mi Kwon, Andrew M Taverner, Laura Kors, Matthew L Aardema, Julia C Holder, Lin Poyraz, Patrick F Reilly, Takashi Kiuchi, Peter Andolfatto","doi":"10.1101/2025.08.10.669386","DOIUrl":"10.1101/2025.08.10.669386","url":null,"abstract":"<p><p>Closely related species often exhibit distinct morphologies that can contribute to species-specific adaptations and reproductive isolation. One example are Lepidopteran caterpillar appendages, such as the \"caudal horn\" of Bombycoidea moths, which have evolved substantial morphological diversity among species in this group. Using interspecific crosses, we identify the genetic basis of the caudal horn size difference between <i>Bombyx mori</i> and its closest relative <i>B. mandarina</i>. The three largest of eight QTL account for one third the mean horn length difference between the species. The largest of these, on chromosome 4, encompasses a conserved <i>Wnt</i>-family gene cluster, key upstream regulators that are well-known for their roles in morphological diversification in animals. Using allele-specific expression analysis and CRISPR/Cas9 knockouts, we show that tissue-specific cis-regulatory changes to <i>Wnt1</i> and <i>Wnt6</i> contribute to the species difference in caudal horn size. This kind of modularity enables highly pleiotropic genes, including key upstream growth regulators, to contribute to the evolution of morphological traits without causing widespread deleterious effects.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12363878/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144884778","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ARID1A and ARID1B preserve B cell identity, prevent myeloid transformation and reveal therapeutic vulnerabilities.","authors":"Phyo Nay Lin, Joohyung Park, Yoon-A Kang, George P Souroullas","doi":"10.1101/2025.09.16.676393","DOIUrl":"10.1101/2025.09.16.676393","url":null,"abstract":"<p><p>Chromatin remodeling by the SWI/SNF complex is essential for hematopoietic lineage commitment and differentiation. While core subunits <i>ARID1A</i> and <i>ARID1B</i> are frequently mutated in B cell malignancies, their functions remain unclear. Recent work established ARID1A-dependent functions within germinal center (GC) B cells, but its role during early B cell development, and whether its homolog, ARID1B, contributes distinct or compensatory roles at steady state or during transformation, remain unknown. Here, we used CD19-Cre-mediated deletion initiated at the pro-B cell stage to investigate their role in B cell development <i>in vivo</i>. Loss of either gene partially blocked B cell differentiation, reducing immature/recirculating B cell output, and impaired germinal center formation following antigen challenge. Combined deletion further reduced peripheral B cells, shortened survival, and resulted in aggressive leukemia. Unexpectedly, the malignancy was of myeloid origin and arose from a subset of CD19-expressing multipotent progenitors (MPPs). <i>Arid1a</i>/<i>Arid1b</i>-deficient MPPs exhibited abnormal expansion, reduced colony formation, and dysregulation of stemness and lineage-priming programs, including diminished CBFA2T3 (ETO2) and Fli1 signatures. In established B cell lymphoma cells <i>in vitro</i>, double ARID1A/ARID1B loss modestly affected cell growth, whereas loss of ARID1A increased sensitivity to EZH2 inhibition. Transcriptomic analyses revealed alterations in cell adhesion/migration pathways, cytokine-receptor interactions and DNA repair mechanisms. Collectively, these findings reveal stage-specific and compensatory roles for ARID1A and ARID1B in B cell development, uncover a mechanism by which SWI/SNF loss in MPPs redirects transformation towards myeloid leukemia, and suggest context-dependent therapeutic vulnerabilities.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12458438/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145152792","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recovery of retinal terminal fields after traumatic brain injury: evidence of collateral sprouting and sexual dimorphism.","authors":"Athanasios S Alexandris, Jaeyoon Yi, Chang Liu, Joseph Belamarich, Zahra Alam, Abhishek Vats, Anthony Peng, Derek S Welsbie, Donald J Zack, Vassilis E Koliatsos","doi":"10.1101/2025.05.28.656451","DOIUrl":"10.1101/2025.05.28.656451","url":null,"abstract":"<p><p>The central nervous system is characterized by its limited regenerative potential, yet striking examples of functional recovery after injury in animal models and humans highlight its capacity for repair. Little is known about repair of pathways/circuits after traumatic brain injury (TBI), which results in disruption of connectivity. Here we utilize a mouse model of diffuse traumatic axonal injury (Impact-acceleration TBI) in order to explore, for the first time, the evolution of structural and functional changes in the terminal fields of the injured visual system. Retinal ganglion cell (RGC) axons and synapses were genetically labeled via AAV transduction, while anterograde and transsynaptic tracers were used to mark terminals and postsynaptic cells. Functional connectivity and visual integrity were assessed by monitoring c-Fos expression following light stimulation and pattern-reversal visual evoked potentials (pVEPs). Our findings demonstrate that, although TAI results in approximately a 50% loss of RGC axons and terminals, surviving RGCs undergo collateral sprouting, a form of compensatory branching of surviving axons, that restores terminal density to pre-injury levels. Transsynaptic tracing and c-Fos mapping confirmed the reestablishment of connectivity, which was also associated with significant improvements in visual function as measured by pVEPs. Interestingly, the recovery process exhibited sexual dimorphism, with female mice showing delayed or incomplete repair. Moreover, collateral sprouting proceeded normally in <i>Sarm1</i> knockout mice, evidence of some independence from Wallerian degeneration. Our findings show that collateral sprouting may be an important mechanism of circuit repair in TAI and may represent a promising target for therapeutic interventions.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12201153/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144510198","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A switch in kappa opioid receptor signaling from inhibitory to excitatory induced by stress in a subset of cortically-projecting dopamine neurons.","authors":"Elyssa B Margolis","doi":"10.1101/2025.08.09.669424","DOIUrl":"10.1101/2025.08.09.669424","url":null,"abstract":"<p><strong>Background: </strong>The kappa opioid receptor (KOR) has shown potential as a therapeutic target for several neuropsychiatric disorders including major depressive disorder, chronic pain, and substance use disorder. Signaling of G protein coupled receptors (GPCRs) like the KOR is generally thought to change in magnitude, not valence, with behavior states. Here we investigated KOR modulation of ventral tegmental area (VTA) neurons following an acute, behaviorally aversive manipulation.</p><p><strong>Methods: </strong>KOR agonist responses were measured with whole cell recordings in acute brain slices containing the VTA from male and female rats. Slices were made <1 hr, 3 days or 5 days after a foot shock or sham session. Slices from untreated rats were used to determine the mechanism of action. Recordings were also made in neurons labeled by the retrograde tracer DiI to evaluate circuit specificity. Place conditioning to intra-VTA KOR agonist injections was performed in sham vs shock rats.</p><p><strong>Results: </strong>After acute stress KOR activation excited a subset of VTA dopamine neurons. In slices from untreated animals, brief corticotrophin releasing factor (CRF) exposure <i>ex vivo</i> rapidly induced a similar switch in KOR signaling. This effect was observed specifically in dorsal medial prefrontal cortex (dmPFC) projecting VTA neurons, but not in other projections. Behaviorally, foot shock stress produced a loss of conditioned place aversion to intra-VTA KOR activation.</p><p><strong>Conclusions: </strong>After acute aversive stress, KOR activation in the VTA excites, rather than inhibits, dmPFC-projecting VTA dopamine neurons. This change can be generated by activating the CRF system and interferes with the aversiveness of VTA KOR activation.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12424744/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145067355","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Human Genome REWRITE for Off-the-Shelf Stem Cells Reveals an \"Epigenetic Ghost\".","authors":"Serena F Generoso, Sarah Levovitz, Susanna Jaramillo, Minjoo Kim, Sumanth Dara, Shean Fu Phen, Bryan Yi, Tomoki Yanagi, Thomas L DesMarais, Neta Agmon, Megan S Hogan, Leslie A Mitchell, David M Truong","doi":"10.1101/2025.09.16.676382","DOIUrl":"10.1101/2025.09.16.676382","url":null,"abstract":"<p><p>Human leukocyte antigen (HLA) polymorphism hinders off-the-shelf cell therapies. We developed REWRITE, a modular platform for iterative, scar-minimized genome writing of synthetic constructs >100 kb in human pluripotent stem cells (hPSCs). Using REWRITE, we deleted 105-209 kb of the HLA locus and installed synthetic 24 kb or 100 kb HLA haplotypes, and a 62 kb antigen-processing locus. This uncovered a persistent, heritable \"epigenetic ghost\" - an active state lingering despite genetic removal - whose resolution to a silenced default state is driven by native intergenic DNA. These loci restored inducible expression in key lineages, sparing cells from NK-mediated killing and establishing HLA-matched T-cell tolerance, enabling off-the-shelf cell therapies. REWRITE facilitates extensible programming of multigenic functions in allogeneic human cells - from immune design to genome architecture discovery.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12458296/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145153032","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fast Ripple-Delta Coupling as Early Biomarker for Post-Traumatic Epileptogenesis in Repetitive Brain Injury.","authors":"Oleksii Shandra, Dzenis Mahmutovic, Biswajit Maharathi, Md Adil Arman, Michael J Benko, Owen Leitzel, Pritom Kumar Saha, Stefanie Robel","doi":"10.1101/2025.09.16.676387","DOIUrl":"10.1101/2025.09.16.676387","url":null,"abstract":"<p><p>Traumatic brain injury (TBI) can induce post-traumatic epilepsy (PTE), but early biomarkers for epileptogenesis are lacking. We used a repetitive diffuse TBI (rdTBI) model in mice with continuous video-EEG monitoring up to 4½ months post-injury to investigate electrographic biomarkers before and during post-traumatic seizure development. 25% of mice developed post-traumatic seizures with highly variable latency (5-126 days post-injury). Most significantly, we identified fast ripple-delta DOWN state coupling as an early biomarker that was detectable at 4 days post-TBI and appeared before seizure onset in all seizure-experiencing mice. This EEG signature distinguished seizure-experiencing from seizure-free TBI mice with high specificity. Power spectrum analysis revealed elevated delta and theta power, reduced physiological fast oscillations (alpha, beta, gamma) and increased pathological high-frequency oscillations (fast ripples) in seizure-experiencing animals, indicating network hyperexcitability. Spike analysis showed that while TBI itself increased cortical excitability, seizure onset triggered a dramatic further escalation in interictal activity. These electrographic signatures were remarkably consistent across all seizure-experiencing animals regardless of single or recurrent seizure pattern. Our results demonstrate that fast ripple-delta coupling represents a promising early biomarker detectable at 4 days post-TBI, before seizure onset, offering potential for early identification of post-traumatic seizure susceptibility. Importantly, this biomarker identified all seizure-prone animals regardless of whether they developed single or recurrent seizures, suggesting shared underlying mechanisms and clinical relevance for any post-traumatic seizure occurrence. These findings emphasize the utility of temporal EEG analysis for detecting early electrographic changes in post-traumatic epileptogenesis and may inform future intervention strategies.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12458357/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145152677","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Distinct System-Level Computations Underlie Perception Differences Throughout the Visual Field.","authors":"Shutian Xue, Antoine Barbot, Jared Abrams, Qingyuan Chen, Marisa Carrasco","doi":"10.1101/2025.09.19.677418","DOIUrl":"10.1101/2025.09.19.677418","url":null,"abstract":"<p><p>Human visual perception for basic dimensions varies with eccentricity and polar angle, influencing daily activities such as reading, searching and scene perception. We investigated whether and how system-level computations that transform visual input into perception underlie these heterogeneities. Using the equivalent noise method and perceptual template model, we estimated gain, internal noise, and nonlinearity for orientation discrimination across eccentricity (fovea, parafovea and perifovea) and around polar angle. Participants discriminated the orientation of Gabors embedded in dynamic white noise and showed the expected variations across eccentricity and around polar angle. Importantly, visual performance declined with eccentricity due to decreased gain and nonlinearity and increased internal noise. Observers with stronger eccentricity effects showed greater gain decrease. Only gain varied with polar angle-higher along the horizontal than vertical meridian, and lower than upper vertical meridian-paralleling performance asymmetries. This dissociation aligns with known variations in neuronal count and tuning, suggesting that neural correlations and neural noise contribute to these system-level computations. By revealing distinct system-level computations underlying the eccentricity effect and polar angle asymmetries, our findings link perceptual heterogeneity across the visual field and neural architecture and provide insights into how the human brain encodes information under neural constraints.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12458108/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145153137","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A hardwired neural circuit for temporal difference learning.","authors":"Malcolm G Campbell, Yongsoo Ra, Zhiqin Chen, Shudi Xu, Mark Burrell, Sara Matias, Mitsuko Watabe-Uchida, Naoshige Uchida","doi":"10.1101/2025.09.18.677203","DOIUrl":"10.1101/2025.09.18.677203","url":null,"abstract":"<p><p>The neurotransmitter dopamine plays a major role in learning by acting as a teaching signal to update the brain's predictions about rewards. A leading theory proposes that this process is analogous to a reinforcement learning algorithm called temporal difference (TD) learning, and that dopamine acts as the error term within the TD algorithm (TD error). Although many studies have demonstrated similarities between dopamine activity and TD errors^1-5, the mechanistic basis for dopaminergic TD learning remains unknown. Here, we combined large-scale neural recordings with patterned optogenetic stimulation to examine whether and how the key steps in TD learning are accomplished by the circuitry connecting dopamine neurons and their targets. Replacing natural rewards with optogenetic stimulation of dopamine axons in the nucleus accumbens (NAc) in a classical conditioning task gradually generated TD error-like activity patterns in dopamine neurons by specifically modifying the task-related activity of NAc neurons expressing the D1 dopamine receptor (D1 neurons). In turn, patterned optogenetic stimulation of NAc D1 neurons in naïve animals drove dopamine neuron spiking according to the TD error of the stimulation pattern, indicating that TD computations are hardwired into this circuit. The transformation from D1 neurons to dopamine neurons could be described by a biphasic linear filter, with a rapid positive and delayed negative phase, that effectively computes a temporal difference. This finding suggests that the time horizon over which the TD algorithm operates-the temporal discount factor-is set by the balance of the positive and negative components of the linear filter, pointing to a circuit-level mechanism for temporal discounting. These results provide a new conceptual framework for understanding how the computations and parameters governing animal learning arise from neurobiological components.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12458361/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145152638","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Response of UBR-box E3 ubiquitin ligases and protein quality control pathways to perturbations in protein synthesis and skeletal muscle size.","authors":"Leslie M Baehr, Luis Gustavo Oliveira de Sousa, Craig A Goodman, Adam P Sharples, David S Waddell, Sue C Bodine, David C Hughes","doi":"10.1101/2025.07.23.666188","DOIUrl":"10.1101/2025.07.23.666188","url":null,"abstract":"<p><p>The N-degron pathway contributes to proteolysis by targeting N-terminal residues of destabilized proteins via E3 ligases that contain a UBR-box domain. Emerging evidence suggests the UBR-box family of E3 ubiquitin ligases (UBR1-7) are involved in the positive regulation of skeletal muscle mass. The purpose of this study was to explore the role of UBR-box E3 ubiquitin ligases under enhanced protein synthesis and skeletal muscle growth conditions. Cohorts of adult male mice were electroporated with constitutively active Akt (Akt-CA) or UBR5 RNAi constructs with a rapamycin diet intervention for 7 and 30 days, respectively. In addition, the UBR-box family was studied during the regrowth phase post nerve crush induced inactivity. Skeletal muscle growth with Akt-CA or regrowth following inactivity increased protein abundance of UBR1, UBR2, UBR4, UBR5 and UBR7. This occurred with corresponding increases in Akt-mTORC1/S6K and MAPK/p90RSK signaling and protein synthesis. The increases in UBR-box E3s, ubiquitination, and proteasomal activity occurred independently of mTORC1 activity and were associated with increases in markers related to autophagy, ER-stress, and protein quality control pathways. Finally, while UBR5 knockdown (KD) evokes atrophy, it occurs together with hyperactivation of mTORC1 and protein synthesis. In UBR5 KD muscles, we identified an increase in protein abundance for UBR2, UBR4 and UBR7, which may highlight a compensatory response to maintain proteome integrity. Future studies will seek to understand the role of UBR-box E3s towards protein quality control in skeletal muscle plasticity.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12330723/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144802324","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CD11c+ Tbet+ B cells constrain obesity- and vaccination-induced germinal center B cells and T helper cells.","authors":"Carlo Vanz, Benjamin T Enslow, Emma Collins, Madilyn Dominguez-Lowry, Nathaniel Liendo, Elizabeth A Dudley, Elizabeth A Leadbetter","doi":"10.1101/2025.09.01.673552","DOIUrl":"10.1101/2025.09.01.673552","url":null,"abstract":"<p><p>Obesity is a rapidly growing public health crisis associated simultaneously with increased metabolic disease and humoral immune suppression to vaccination or infection. Inflammatory CD11c+T-bet+ B cells increase in spleen and adipose tissue during obesity and exacerbate metabolic dysfunction via antibodies. We now find that during obesity Tbet+ B cells also expand in the liver but not omentum or mesenteric fat. Obese mice also develop increased splenic CXCR5+ T_FH and hepatic CXCR5- T_PH cells which serve as likely partners for antigen-experienced MHC-II+ CD11c+ Tbet+ B cells. We also observed that antibodies in obese mice, previously found to contribute to metabolic disease, largely circulate as inflammatory autoantigen-bound immune complexes. Obese mice lacking T-bet in B cells also develop increased autoantibody titers and expanded splenic germinal center (GC) B and T helper cells. T-bet+ B cell-deficient mice make a similarly enhanced GC, T_FH, T_PH response to haptenated-protein vaccination with a corresponding increase in antibody affinity, although there is no additive effect of obesity. These results are consistent with GC inhibition by expanded CD11c+ B cells demonstrated by others to occur during autoimmunity, suggesting a broadly universal mechanism which may explain reduced humoral immunity and poor clinical outcomes following infection in patients with obesity and other forms of chronic inflammation.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12424663/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145067342","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}