Differential Requirement for Dimerization of the Membrane-Binding PH–TH Module of BTK in B cells and T cells DOI Creative Commons
Timothy J. Eisen, Sam Ghaffari-Kashani, Jay T. Groves

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Oct. 6, 2023

Abstract Bruton’s tyrosine kinase (BTK) is a major drug target in immune cells. The membrane-binding pleckstrin-homology and tec-homology (PH–TH) domains of BTK are required for signaling. In vitro, dimerization the PH–TH module strongly stimulates activity. Whether dimerizes cells via module, whether this necessary signaling, unknown. To address question, we developed high-throughput mutagenesis assays function B T We measured fitness costs thousands point mutations domain, allowing us to assess activity function. Ramos find that neither nor Instead, cells, signaling enhanced by increase membrane adsorption, even at cost reduced dimerization. contrast, Jurkat depends on both Evolutionary analysis shows proteins fish lower organisms, like all Tec kinases other than BTK, lack but have active domains. Thus, not intrinsically Tec-kinase activity, special feature evolved exert stricter regulatory control as adaptive systems gained increased complexity.

Language: Английский

The melano-macrophage: The black leukocyte of fish immunity DOI Creative Commons
Håvard Bjørgen, Erling Olaf Koppang

Fish & Shellfish Immunology, Journal Year: 2024, Volume and Issue: 148, P. 109523 - 109523

Published: March 24, 2024

Melanin and the process of melanin synthesis or melanogenesis have central roles in immune system insects, production melanin-synthesizing enzymes from their haemocytes may be induced following activation through danger signals. Melanin-containing macrophage-like cells been extensively studied amphibians they are also present reptiles. In fish, melano-macrophages especially recognized with respect to melano-macrophage centres (MMCs), hypothesized analogues germinal secondary lymphoid organs mammals some birds. Melano-macrophages addition several inflammatory conditions, particular melanised focal changes, black spots, musculature farmed Atlantic salmon, Salmo salar. Melanins complex compounds that divided into different forms which all ability absorb scatter light. Other functions include quenching free radicals a direct effect on system. According common view held pigment cell community, vertebrate melanosome formation only occur ectodermal origin. However, abundant information suggests myeloid ectothermic vertebrates classified as melanocytes. Here, we discuss these opposing views review relevant literature. Finally, current status research concerning muscle changes represent most severe quality problem Norwegian salmon production, but other diseases where play important roles.

Language: Английский

Citations

13
The fish spleen DOI Creative Commons
A. Zapata

Fish & Shellfish Immunology, Journal Year: 2023, Volume and Issue: 144, P. 109280 - 109280

Published: Dec. 10, 2023

In the present study, we review structure and function of fish spleen with special emphasis on its condition in Elasmobranchs, Teleosts Lungfish. Apart from amount splenic lymphoid tissue, histological organization organ ensures existence areas involved antigen trapping, ellipsoids, exhibit numerous melano-macrophages which appear isolated or forming so-called melano-macrophage centres. An extensive discussion functional significance these centres conclude that they are mere accumulations macrophages consequence tissue homeostasis rather than primitive germinal centres, as proposed by some authors.

Language: Английский

Citations

22
Cell atlas of the Atlantic salmon spleen reveals immune cell heterogeneity and cell-specific responses to bacterial infection DOI Creative Commons
Jianxuan Sun, Rose Ruiz Daniels, Adam Balic

et al.

Fish & Shellfish Immunology, Journal Year: 2024, Volume and Issue: 145, P. 109358 - 109358

Published: Jan. 3, 2024

The spleen is a conserved secondary lymphoid organ that emerged in parallel to adaptive immunity early jawed vertebrates. Recent studies have applied single cell transcriptomics reveal the cellular composition of several species, cataloguing diverse immune types and subpopulations. In this study, 51,119 nuclei transcriptomes were comprehensively investigated commercially important teleost Atlantic salmon (Salmo salar L.), contrasting control animals with those challenged bacterial pathogen Aeromonas salmonicida. We identified clusters representing expected major types, namely T cells, B natural killer-like granulocytes, mononuclear phagocytes, endothelial mesenchymal erythrocytes thrombocytes. discovered heterogeneity within lineages, providing evidence for resident macrophages melanomacrophages, infiltrating monocytes, candidate dendritic subpopulations, cells at distinct stages differentiation, including plasma an igt + subset. provide twelve subsets, cd4+ helper regulatory one cd8+ subset, three γδT populations double negative cd4 cd8. number genes showing differential expression during infection was highly variable across largest changes observed followed by resting mature cells. Our analysis provides local inflammatory response alongside maturation spleen, upregulation ccr9 consistent recruitment gut deal infection. Overall, study new cell-resolved perspective actions highlighting extensive hidden bulk transcriptomics. further large catalogue cell-specific marker can be leveraged explore function structural organization salmonid system.

Language: Английский

Citations

7
The axillary lymphoid organ is an external, experimentally accessible immune organ in the zebrafish DOI
Daniel Castranova, Madeleine I. Kenton, Aurora Kraus

et al.

The Journal of Experimental Medicine, Journal Year: 2025, Volume and Issue: 222(6)

Published: March 4, 2025

Lymph nodes and other secondary lymphoid organs play critical roles in immune surveillance activation mammals, but the deep internal locations of these make it challenging to image study them living animals. Here, we describe a previously uncharacterized external organ zebrafish ideally suited for studying cell dynamics vivo, axillary (ALO). This small, translucent has an outer cortex teeming with cells, inner medulla mesh-like network fibroblastic reticular cells along which migrate, lymphatic vessels draining large adjacent lymph sac. Noninvasive high-resolution imaging transgenically marked can be carried out ALOs animals, are readily accessible treatment. newly discovered tissue provides superb model dynamic live their interaction pathogens surrounding tissues, including blood vessels.

Language: Английский

Citations

1
The unexpected role of nurse shark pancreas as a secondary lymphoid organ DOI Creative Commons
Thomas Hill, Helen Dooley

The Journal of Immunology, Journal Year: 2025, Volume and Issue: unknown

Published: May 15, 2025

Abstract Secondary lymphoid organs (SLOs) provide a structured environment to facilitate interactions between low frequency antigen-specific B and T cells as well cognate antigen displayed by presenting (APCs), resulting in the initiation of effective adaptive immune responses. The spleen is most evolutionary ancient SLO, emerging concurrently with immunity an early jawed vertebrate ancestor. In mammals, immunoprotective role complemented that other SLOs, notably network draining lymph nodes gut-associated tissue (GALT) screen for infections throughout host. However, are only present endothermic vertebrates (ie, mammals possibly some birds), so it unclear how majority species maintain robust surveillance their entire body produce timely efficacious antibody While investigating responses nurse shark, cartilaginous fish (Chondrichthyes) which last shared common ancestor ∼450 million yr ago, we discovered pancreas contains cell follicles spatially distinct from exocrine endocrine pancreas. Furthermore, these “pancreatic follicles” exhibit many hallmarks selection previously identified shark spleen. Our results also demonstrate antibodies produced within following immunization. study supports designation SLO provides insight into may function absence nodes.

Language: Английский

Citations

1
Understanding vertebrate immunity through comparative immunology DOI
Thomas Boehm

Nature reviews. Immunology, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 24, 2024

Language: Английский

Citations

3
Conditional requirement for dimerization of the membrane-binding module for BTK signaling in lymphocyte cell lines DOI
Timothy J. Eisen, Sam Ghaffari-Kashani, Chien‐Lun Hung

et al.

Science Signaling, Journal Year: 2025, Volume and Issue: 18(869)

Published: Jan. 14, 2025

Bruton’s tyrosine kinase (BTK) is a major drug target in immune cells. The membrane-binding pleckstrin homology and tec (PH-TH) domains of BTK are required for signaling. Dimerization the PH-TH module strongly stimulates activity vitro. Here, we investigated whether dimerizes cells using this dimerization necessary To address question, developed high-throughput mutagenesis assays function Ramos B Jurkat T We measured fitness costs thousands point mutations domain to assess were function. In cells, found that neither nor was Instead, signaling enhanced by increased membrane adsorption, even at cost reduced dimerization. contrast, depended on both activity. Evolutionary analysis indicated proteins organisms evolved before divergence ray-finned fishes lacked but had active domains, similar other Tec family kinases. Thus, distinct feature exert stricter regulatory control as adaptive systems gained complexity.

Language: Английский

Citations

0
Memory responses to ovalbumin-immunization in Mojave desert tortoises DOI
Franziska C. Sandmeier,

Kiara Olson,

Angelina Martin

et al.

Developmental & Comparative Immunology, Journal Year: 2025, Volume and Issue: unknown, P. 105322 - 105322

Published: Jan. 1, 2025

Language: Английский

Citations

0
The Importance of Monitoring Antigen-Specific Memory B Cells, and How ImmunoSpot Assays Are Suitable for This Task DOI Creative Commons
Greg A. Kirchenbaum, Graham Pawelec,

Paul Lehmann

et al.

Cells, Journal Year: 2025, Volume and Issue: 14(3), P. 223 - 223

Published: Feb. 5, 2025

Determining an individual’s humoral immune reactivity to a pathogen, autoantigen, or environmental agent is traditionally accomplished through the assessment of specific antibody levels in blood. However, many instances, titers antibodies decline over time and thus do not faithfully reveal prior antigen exposure establishment immunological memory. To estimate competence, it therefore necessary assess functional B cell Here, we describe novel ELISPOT FluoroSpot assays (collectively referred as ImmunoSpot) that can be rapidly developed validated characterize memory (Bmem) repertoire for any desired ex vivo at single-cell resolution. Moreover, multiplexed variants assay enable high-throughput testing antigen-specific cells secreting distinct classes and/or IgG subclasses, with minimal material requirements. ImmunoSpot also measurement affinity distributions within Bmem compartment permit cross-reactivity measurements provide insights into established against future pathogen variants. Collectively, ImmunoSpot® system presented here highly reproducible, readily regulated tests. The newly gained ability monitor should catalyze more comprehensive understanding immunity health disease.

Language: Английский

Citations

0
Recent Advances in Understanding the Immune System of Reptiles DOI
Franziska C. Sandmeier

Elsevier eBooks, Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 1, 2024

Language: Английский

Citations

2