Top 5 Biorxiv Papers Today in Immunology


2.001 Mikeys
#1. Polypyrimidine Tract Binding Proteins are essential for B cell development
Elisa Monzon-Casanova, Louise S. Matheson, Kristina Tabbada, Kathi Zarnack, Christopher W. J. Smith, Martin Turner
During B cell development, recombination of immunoglobulin loci is tightly coordinated with the cell cycle to avoid unwanted rearrangements of other genomic locations. Several factors have been identified that suppress proliferation in late-pre-B cells to allow light chain recombination. By comparison, our knowledge of factors limiting proliferation during heavy chain recombination at the pro-B cell stage is very limited. Here we identify an essential role for the RNA-binding protein Polypyrimidine Tract Binding Protein 1 (PTBP1) in B cell development. Absence of PTBP1 and the paralog PTBP2 results in a complete block in development at the pro-B cell stage. PTBP1 promotes the fidelity of the transcriptome in pro-B cells. In particular, PTBP1 controls a cell cycle mRNA regulon, suppresses entry into S-phase and promotes progression into mitosis. Our results highlight the importance of S-phase entry suppression and post-transcriptional gene expression control by PTBP1 in pro-B cells for proper B cell development.
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MonzonCasanova: Excited to share our preprint showing an essential role for the RNA-binding protein PTBP1 during B cell development: https://t.co/MrnCu3CpBd 1/2 https://t.co/LJ9AYqJKEr
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Authors: 6
Total Words: 18058
Unqiue Words: 3872

1.997 Mikeys
#2. A dynamic interaction between CD19 and the tetraspanin CD81 controls B cell co-receptor trafficking
Katherine J. Susa, Tom C.M. Seegar, Stephen C. Blacklow, Andrew Kruse
CD81 and its binding partner CD19 are core subunits of the B cell co-receptor complex. While CD19 is a single-pass transmembrane protein belonging to the extensively studied Ig superfamily, CD81 belongs to a conserved but poorly understood family of four-pass transmembrane proteins called tetraspanins. These functionally diverse proteins play important roles in a wide variety of different organ systems by controlling protein trafficking and other cellular processes. Here, we show that CD81 relies on its ectodomain to control trafficking of CD19 to the cell surface. Moreover, the anti-CD81 antibody 5A6, which binds selectively to activated B cells, recognizes a conformational epitope on CD81 that is masked when CD81 is in complex with CD19. Mutations of CD81 in this contact interface suppress its CD19 surface-export activity. Taken together, these data indicate that the CD81 - CD19 interaction is dynamically regulated upon B cell activation, suggesting that this dynamism can be exploited to regulate B cell function. These results...
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biorxivpreprint: A dynamic interaction between CD19 and the tetraspanin CD81 controls B cell co-receptor trafficking https://t.co/RhZ36UMHvC #bioRxiv
biorxiv_immuno: A dynamic interaction between CD19 and the tetraspanin CD81 controls B cell co-receptor trafficking https://t.co/NxJr5LTnMV #biorxiv_immuno
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Authors: 4
Total Words: 0
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1.997 Mikeys
#3. Progressive differentiation of memory CD8 T cells in the cervicovaginal tissue
Veronica Dave, Erwing Fabian Cardozo Ojeda, Florian Mair, Jami Erickson, Amanda Woodward-Davis, Andrew Soerens, Julie Czartoski, Candice Teague, Susanne Oberle, Dietmar Zehn, Joshua Schiffer, Jennifer M Lund, Martin Prlic
The memory CD8 T cell compartment in human cervicovaginal tissue (CVT) is phenotypically and functionally distinct compared to other non-lymphoid tissues. To determine if these distinctive features are driven by residence in the tissue itself, rather than a consequence of local antigenic insults, we used a mouse model to assess memory CD8 T cell differentiation in the CVT. Following systemic immunization to elicit a CD8 T cell response to a herpes simplex virus (HSV) epitope, HSV-specific memory CD8 T cells were stably maintained in other tissues but gradually declined in the CVT over 5 months post-immunization, correlating with a delay in viral control upon HSV challenge. While memory cells in the periphery and small intestine maintained a fairly stable phenotype after 30 days, memory CD8 T cells in the CVT gradually acquired a CD103+, TCF-1-, granzyme B+ phenotype over the 5 month time span. Notably, a sizable and phenotypically similar population of CD8 T cells was also found in human CVT. Our data indicate that the CVT...
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biorxivpreprint: Progressive differentiation of memory CD8 T cells in the cervicovaginal tissue https://t.co/NGl913iXSI #bioRxiv
biorxiv_immuno: Progressive differentiation of memory CD8 T cells in the cervicovaginal tissue https://t.co/bik18ovmgh #biorxiv_immuno
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Authors: 13
Total Words: 12575
Unqiue Words: 3752

1.997 Mikeys
#4. Inosine is an alternative carbon supply that supports effector T cell proliferation and anti-tumor function under glucose restriction
Tingting Wang, JN Rashida Gnanaprakasam, Xuyong Chen, Siwen Kang, Xuequn Xu, Hua Sun, Lingling Liu, Ethan Miller, Teresa A. Cassel, Qiushi Sun, Sara Vicente-Munoz, Marc O. Warmoes, Andrew N. Lane, Xiaotong Song, Teresa W.-M. Fan, Ruoning Wang
T cells undergo a characteristic metabolic rewiring that fulfills the dramatically increased bioenergetic, biosynthetic, and redox demands following antigen stimulation. A robust adaptive immune system requires effector T cells to respond and adapt to fluctuations in environmental nutrient levels imposed by infectious and inflammatory sites in different tissues. Inevitably, such responsiveness and adaptation reflect metabolic plasticity, allowing T cells to elicit immune functions by using a wide range of nutrient substrates. Here, we show that effector T cells utilize inosine, as an alternative substrate, to support cell growth and function in the absence of glucose. T cells metabolize inosine into hypoxanthine and phosphorylated ribose by purine nucleoside phosphorylase (PNP). Using Stable Isotope-Resolved Metabolomics (SIRM), we demonstrated that ribose moiety of inosine can enter into central metabolic pathways to provide ATP and biosynthetic precursors. Accordingly, the dependence of T cells on extracellular glucose for...
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biorxivpreprint: Inosine is an alternative carbon supply that supports effector T cell proliferation and anti-tumor function under glucose restriction https://t.co/0m2QvPNCbs #bioRxiv
biorxiv_immuno: Inosine is an alternative carbon supply that supports effector T cell proliferation and anti-tumor function under glucose restriction https://t.co/hO3w8jpSDa #biorxiv_immuno
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Authors: 16
Total Words: 0
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1.997 Mikeys
#5. Lack of apolipoprotein A1 impairs optimal regulatory T cell homeostasis at steady state due to impaired IL-2 signaling
Dalia E. Gaddis, Runpei Wu, John S. Parks, Mary G. Sorci-Thomas, Catherine C. Hedrick
Apolipoprotein A1 (ApoA1), the major constituent of the high-density lipoprotein (HDL) molecule, exhibits anti-inflammatory properties. Our laboratory has previously shown that ApoA1 protects against switching of regulatory T (Treg) cells to atherogenic T follicular helper cells in Western diet-fed mice. However, the role of ApoA1 in modulating Treg cell homeostasis in the absence of atherosclerosis remains uncharacterized. Here, we show that ApoA1 is required for normal Treg cell homeostasis and functioning at steady state. Specifically, lack of ApoA1 decreased the numbers of both natural and induced Treg cells and also lowered Treg cell-based homeostatic proliferation and suppressive functions. Importantly, these changes occurred without affecting other T cell populations. Finally, we determined that the observed phenotypes were caused by changes to cholesterol content and reduced interleukin-2 (IL-2) receptor signaling in ApoA1-deficient Treg cells. Overall, our results show that ApoA1-HDL is necessary for Treg cell homeostasis...
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biorxivpreprint: Lack of apolipoprotein A1 impairs optimal regulatory T cell homeostasis at steady state due to impaired IL-2 signaling https://t.co/cXdtuph98G #bioRxiv
biorxiv_immuno: Lack of apolipoprotein A1 impairs optimal regulatory T cell homeostasis at steady state due to impaired IL-2 signaling https://t.co/UOOdMhFb27 #biorxiv_immuno
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Authors: 5
Total Words: 5757
Unqiue Words: 1690

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