What are B cells and why do they matter? | Lokesh Upadhyay posted on the topic | LinkedIn (2024)

In this week’s #MAbMonday spotlight, we’d like to recognize the work on Interleukin-2 signals converge in a lymphoid–dendritic cell pathway that promotes anticancer immunity.https://hubs.la/Q027TXRp0The team stated, "We found that interleukin-2 (IL-2) stimulated DC formation through innate and adaptive lymphoid cells in mice and humans, and this increase in DCs improved anticancer immunity. Administration of IL-2 to humans within a clinical trial and of IL-2 receptor (IL-2R)–biased IL-2 to mice resulted in pronounced expansion of type 1 DCs, including migratory and cross-presenting subsets, and type 2 DCs, although neither DC precursors nor mature DCs had functional IL-2Rs. In mechanistic studies, IL-2 signals stimulated innate lymphoid cells, natural killer cells, and T cells to synthesize the cytokines FLT3L, CSF-2, and TNF. These cytokines redundantly caused DC expansion and activation, which resulted in improved antigen processing and correlated with favorable anticancer responses in mice and patients. Thus, IL-2 immunotherapy–mediated stimulation of DCs contributes to anticancer immunity by rendering tumors more immunogenic."👇Featured products👇Anti-Mouse CD279 (PD-1) (Clone RMP1-14) – Purified in vivo GOLD™ Functional Grade: https://hubs.la/Q027TQ5S0Anti-Mouse NK1.1 Antibody – Purified in vivo GOLD™ Functional Grade: https://hubs.la/Q027TRwD0#Leinco #ReproducibleScience #Immunology

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Determining the expression profiles of your antigens can be a frustrating process 🔬Yet, understanding the comparative change in protein expression, or antigen density, of your markers is a pivotal step in the panel design process. To help you determine the relative density of your antigens, we’ve aggregated various methods, resources, and community insights in our latest article. https://lnkd.in/g3Dy5VAW#flowcytometry #immunology #cancerresearch

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Receptor-ligand interactions are critical for initiating and sustaining both innate and adaptive immune responses. Understanding how receptors are triggered has historically been fundamental in the characterization of of how immune responses are triggered, adaptively shaped to the evolution of infection and how they are ultimately resolved. Many receptor-ligand interactions, such as those between TCR and pMHC or LFA-1 and ICAMs must occur in trans in order to promote synapse formation and correct synapse architecture. However, new data is starting to shed light on unique mechanisms by which critical immune co-receptors such as CD28 can actually interact with their respective ligands to propagate signaling networks that coordinate, branch and amplify ensuing downstream signals that lead to effector activity. Membrane invagin*tion post TCR-pMHC ligation allows for CD28 to bind its ligand, B7 in cis on the same T cell membrane. Given the paucity of APCs in peripheral tissues, these discoveries provide critical biochemical and cellular mechanisms that explain key steps of T cell activation in peripheral tissues where professional APCs (which express B7 in trans) are typically quite scarce. These observations force us to revise our understanding of how adaptive immune responses are shaped in response to infections and tumor immunity alike and what relevant biomarkers could be in these settings.Similar mechanisms have recently been identified for the co-inhibitory receptor PD-1. Recent reports have shown that PD-1 engagement of PD-L1 on certain tumors or on infiltrating leukocyte sub-populations into the TME can restrict the ability of PD-L1 to engage PD-1 in cis on T cells. Consequentially, T cells exhibit hightened effector and cytolytic activity in these contexts. How we can leverage the importance of cis/trans receptor/ligand interactions to generate therapeutically meaningful advances in the clinic remains to be seen...but no doubt there will be progress. https://lnkd.in/eB6M2h44https://lnkd.in/eiV_QJzu #immunotherapy #immunity #health #diseaseprevention #cancerresearch

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I am thrilled to share with you that our paper describing how to produce and use tetramers to study antigen-specific B cells is finally out in Nature Protocols. The technique we describe here provides enough resolution to detect extremely scarce antigen-specific B lymphocytes, as rare as 1 in 100 million cells, from both mouse and human samples. It also allows us to discriminate between different B cell subtypes, or even different isotypes. We believe that this technique can be helpful for people studying the #immunesystem in many different areas: from #allergy, to #infectiousdiseases, #cancer or #autoimmunity. The first decision is to choose the antigen you would like to study, and then... Hands on working! It has been an incredible and exciting process to put this manuscript together with so many talented co-workers. I would like to say thank you to all of them but, in order to keep this post concise, I will highlight only two names today. Thank you Allyssa Phelps for introducing me to the world of tetramers, being so patient throughout all my questions and doubts, and for being a friend after those long days at the #flowcytometry facilities. And thank you Joshua Koenig for leading this project with so much enthusiasm, for trusting me with it and for reminding me every day why I love #science.

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Harnessing Biomaterials to Amplify Immunity in Aged Mice through T Memory Stem CellsThe durability of a protective immune response generated by a vaccine depends on its ability to induce long-term T cell immunity, which tends to decline in aging populations. The longest protection appears to arise from T memory stem cells (TMSCs) that confer high expandability and effector functions when challenged. Here we engineered artificial antigen presenting cells (aAPC) with optimized size, stiffness and activation signals to induce human and mouse CD8+TMSCsin vitro. This platform was optimized as a vaccine booster of TMSCs (Vax-T) with prolonged release of small-molecule blockade of the glycogen synthase kinase-3β together with target antigens. By using SARS-CoV-2 antigen as a model, we show that a single injection of Vax-T induces durable antigen-specific CD8+TMSCs in young and aged mice, and generates humoral responses at a level stronger than or similar to soluble vaccines. This Vax-T approach can boost long-term immunity to fight infectious diseases, cancer, and other diseases.https://lnkd.in/gSuyV38z

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⏺Screening of components of Lipids for the best LNP optimization. ⏺ A Study Published in Nature Biomedical Engineering on #December11, 2023⏺Here, Prof. @Haiquan Mao team reports a screening method for LNP that optimizes the type and proportion of helper lipids to enhance mRNA for tumor antigen delivery to dendritic cells and their immune activation profiles, thereby enhancing antitumor activity. The method involves screening bone marrow-derived dendritic cells that can enhance in vitro.⏺The study found that the most effective antitumor activity, mainly when used in combination with immune checkpoint inhibitors, is caused by synergistic attack of T cells and NK cellstriggered by LNP.It produces strong immune activity in both type 1 and type 2 T helper cells.⏺In antigen-presenting cells（APC）The internally translated antigens are processed and presented directly to CD8 + T cells, which help activate the cellular immune response. Antigens not translated in APC are internalized by APC and presented to CD4 + T helper cells. This opal mechanism translated within non-APC may also contribute to B-cell differentiation and antibody production. This potent efficacy has been attributed to the adjuvant activity of LNP, particularly their Induction of germinal center formation and T lymphocyte helper（Tfh）reaction. In addition, there are findings that support the idea that LNPs optimized for COVID-19 mRNA vaccines can also generate CD4 + Th1 and CD8 + cell-mediated cellular immunity, which may contribute to generating the Th2 response required for a robust humoral response, resulting in high levels of neutralizing antibodies.Repost and for latest updates on #mRNA delivery

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🔬🔍#NewPublication Alert#EzMate #automated #pipetting #systemIsraeli researchers have introduced FLU-LISA, a novel antigen microarray-based assay for rapid antibody profiling. It offers high specificity and sensitivity when measuring antibody responses using influenza and SARS-CoV-2 antigen microarrays. FLU-LISA allows profiling of hundreds of samples against dozens of antigens in a single day, providing a fast and high-throughput alternative to traditional ELISA for antibody testing. Plus, it requires minimal sample and antigen amounts.To run efficient ELISA with reduced sample volumes and antigens, the researchers optimized their ELISA protocol for 384-well plate format, They utilized EzMate 601 Automated Pipetting System to automate this process, ensuring precise and consistent dispensing of samples.📖 Curious to learn more? Check out the publication by Shlomia Levy et al. in Immunology & Cell Biologyhttps://lnkd.in/gSA8GDKFDiscover how the EzMate can enhance your ELISA experiments 💪🔬https://lnkd.in/dkz8qn5#Publication #ELISA #FLULISA #Automation #Pipetting #EzMate #blueraybio

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Happy Thursday all! Check out this open access Nature Signal Transduction and Targeted Therapy research highlight by Gao et al., "Activated STING: an ion channel to trigger non-interferon-related functions."Summary:"Recently, a study published inScienceby Liu et al.presented compelling evidence demonstrating that upon translocation to the Golgi apparatus, STING (Stimulator of Interferon Genes) serves as a direct mediator for proton release into the cytosol, thereby instigating non-canonical LC3B (light-chain 3B) lipidation and NLRP3 (NOD-like receptor family pyrin domain–containing 3) inflammasome activation (Fig.1). This study offers a new perspective on the involvement of the cGAS-STING pathway in non-interferon-related functions."#drugdiscovery #celldeath #sting #pyroptosis #immunology #scientificresearch #sciencecommunication

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The#PD1/ #PDL1#checkpointpathway is almost exclusively associated with #cancer and #immunotherapies. But there is much more to this pathway, as the review "The role of the immunosuppressive #PD1/ #PDL1checkpoint pathway in the#agingprocess and#agerelateddiseasesEasy IMMUNO-ATMPs Rocket Program

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CD314 at a glanceCD314, also known as NKG2D (natural killer receptor G2D) or KLRK1 (killer cell lectin-like receptor subfamily K, member 1), serves to the immune system as adanger sensor. It is a hom*odimeric C-type lectin-like activating receptor and costimulator with type II membrane orientation (C terminus extracellular). CD314 hom*odimers are associated with DAP10, a membrane adaptor protein that signals similar to CD28 by recruitment of phosphatidylinositol 3-kinase. CD314 is expressed mainly on cytotoxic T cells and NK cells and upon binding to its ligands, itstimulates cytotoxic reactionagainst the target cell. On Tc cells, gamma/delta T cells and other CD314 positive T cell subpopulations it works as a costimulatory receptor, on NK cells it is a primary activating receptor. Under particular conditions CD314 can be induced also on some myeloid cells. CD314 ligandsof MHC class-I family (MICA, MICB) and of RAET1 family (ULBP1-6) are usually expressed on the surface of stressed cells and their presence there is a signal for immunity reaction against these cells. Exposition of CD314 ligands can be induced e.g. by DNA damage, TLR signaling, viral infection, or under specific cytokine conditions, such as in case of inflammation or autoimmunity. It can be also an important signal of tumor cells, however, some cancers are able to remove CD314 ligands from their surface to evade the immune system. One of possible therapeutic strategies is to restore or increase CD314 ligands on tumor cells by irradiation.Although CD314 is a stimulatory receptor, in the immune system it can playcomplex roles. If its ligands appear on antigen presenting cells, it can work as an immunosuppresive factor, if they are present on Treg cells, CD314 can suppress particular immunotolerance mechanism etc. Interestingly, CD314 ligands can be expressed even on NK cells themselves, which seems to represent an inter-NK cell regulatory mechanism.More details available on EXBIO web site HERE:https://lnkd.in/e6eMBaeS#CD314 #UV #antibody #monoclonal #cancer #flowcytometry #immunotolerance #EXBIO #tumor #cytotoxic #immunology #MICA #MICB

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