B-cell receptor (BCR) complexes are expressed on the surface of a B-cell and are critical in antigen recognition and modulating the adaptive immune response. Even though the relevance of antibodies has been known for almost a hundred years, the antigen-dependent activation mechanism of B-cells has remained elusive. Several models have been proposed for BCR activation, including cross-linking, conformation-induced oligomerization, and dissociation activation models. Recently, the first cryo-EM structures of the human B-cell antigen receptor of the IgM and IgG isotypes have been published that validates the asymmetric organization of the BCR complex. Here, we carry out extensive molecular dynamics simulations to probe the conformational changes upon antigen binding and the influence of the membrane lipids. We identify two critical dynamical events that could be associated with antigen-dependent activation of BCR. First, antigen binding causes increased flexibility in regions distal to the antigen binding site. Second, antigen binding alters the rearrangement of IgM transmembrane helices, including the relative interaction of Igα/Igβ that mediates intracellular signaling. Furthermore, these transmembrane rearrangements lead to changes in localized lipid composition. Our work indirectly supports the conformational-change induced models of BCR activation and contributes to the understanding of the antigen-dependent activation mechanism of BCRs. Extensive multiscale modeling of B-cell receptor in the presence and absence of a model antigen in a complex membrane environment revealed the dynamical events throughout the receptor and surrounding membrane upon antigen binding to the receptor.

University of Melbourne’s Professor Laura Mackay, has been presented with the National Health and Medical Research Council Elizabeth Blackburn Investigator Grant Award for being the highest-ranking female applicant to receive an NHMRC Investigator Grant.

L’équipe de Nathalie Labrecque a découvert que la signalisation NOTCH est essentielle à la différenciation des lymphocytes T CD8+, optimisant leur réponse immunitaire aux infections.

So interesting study!

In a recent study published in Nature, our scientists discovered that IL-27 — an important signaling protein that regulates immune responses — can boost the… | 27 comments on LinkedIn

Welcome to Saturday Hashtag, a weekly place for broader context.

🔥 Hot off the press!

✨ Super excited to share our latest review just published in the top-tier Journal of Experimental & Clinical Cancer Research! Springer Nature!

👉 Dive into the world of Natural Killer Cells: the Immune Frontline against Circulating Tumor Cells.

📖 Read it here & enjoy: https://lnkd.in/eesgH_JR

✅ It’s open access—free to read and share!
Let’s spread the science! 🚀

Natural killer (NK) play a key role in controlling tumor dissemination by mediating cytotoxicity towards cancer cells without the need of education. These cells are pivotal in eliminating circulating tumor cells (CTCs) from the bloodstream, thus limiting cancer spread and metastasis. However, aggressive CTCs can evade NK cell surveillance, facilitating tumor growth at distant sites. In this review, we first discuss the biology of NK cells, focusing on their functions within the tumor microenvironment (TME), the lymphatic system, and circulation. We then examine the immune evasion mechanisms employed by cancer cells to inhibit NK cell activity, including the upregulation of inhibitory receptors. Finally, we explore the clinical implications of monitoring circulating biomarkers, such as NK cells and CTCs, for therapeutic decision-making and emphasize the need to enhance NK cell-based therapies by overcoming immune escape mechanisms.

👏👏👏 Doryan Masmoudi, Martin Villalba, Catherine Alix-Panabières
CHU de Montpellier, Recherche et innovation – CHU de Montpellier, Renan Targhetta, Samir JABER
Liquid Biopsy LCCRH Lab - Laboratoire Cellules Circulantes Rares Humaines 🩸
European Liquid Biopsy Society (ELBS)
PANCAID, GUIDE.MRD
OncoDaily
Mauro Castelli

#CTC #NK #PrecisionMedicine #LiquidBiopsy #ImmuneEscape

Genome-wide CRISPR screen in human T cells reveals regulators of FOXP3

The RBPJ–NCOR repressor complex is identified as a negative regulator of FOXP3…

Fibrosis: cross-organ biology and pathways to development of innovative drugs

This Review integrates viewpoints of biologists and physician-scientists on core…

B cells have long been understood to be drivers of both humoral and cellular immunity. Recent advances underscore this importance but also indicate that in infection, inflammatory disease and cancer, B cells function directly at sites of inflammation and form tissue-resident memory populations. The spatial organization and cellular niches of tissue B cells have profound effects on their function and on disease outcome, as well as on patient response to therapy. Here we review the role of B cells in peripheral tissues in homeostasis and disease, and discuss the newly identified cellular and molecular signals that are involved in regulating their activity. We integrate emerging data from multi-omic human studies with experimental models to propose a framework for B cell function in tissue inflammation and homeostasis. B cells are major drivers of systemic immunity, but they also act locally in non-lymphoid organs. This Review highlights new insights into mechanisms of tissue B cell function as well as efforts to leverage this biology for immunotherapy.