Somatic Hypermutation Unlocks Antibody Specificities Beyond the Primary Repertoire

Medicine, Rheumatology and Immunology, Life Sciences, Immunology,
somatic hypermutation   antibody specificity   primary repertoire   immune system   antigen recognition  

Academic Background One of the defining features of the adaptive immune system is its ability to generate highly diverse antigen receptors through V(D)J recombination, enabling recognition of a broad range of pathogenic threats. The traditional view holds that somatic hypermutation (SHM) in germinal centers (GCs) can only optimize pre-existing anti...

A Hierarchy of Intestinal Antigens Instructs the CD4+ T Cell Receptor Repertoire

Medicine, Infectious Diseases, Rheumatology and Immunology, Gastroenterology, Life Sciences, Immunology,
intestinal immunity   T cell receptor   microbiota   dietary antigens   inflammatory bowel disease  

I. Research Background The intestinal immune system must balance tolerance and defense against dietary antigens, microbiota-derived antigens, and self-antigens. Although CD4+ T cells are known to play a central role in gut immunity, how different antigen sources shape the composition of the T cell receptor (TCR) repertoire remains unclear. The trad...

Direct Microglia Replacement Reveals Pathologic and Therapeutic Contributions of Brain Macrophages to a Monogenic Neurological Disease

Medicine, Neurology, Life Sciences, Cell Biology, Immunology,
microglia   macrophages   monogenic disease   neuropathology   therapy  

Academic Background Krabbe disease (also known as globoid cell leukodystrophy, GLD) is a fatal pediatric neurodegenerative disorder caused by mutations in the galactosylceramidase (GALC) gene. A hallmark pathological feature of this disease is the presence of lipid-laden globoid cells (GCs) in the central nervous system (CNS). Currently, hematopoie...

Monocytes Can Efficiently Replace All Brain Macrophages and Fetal Liver Monocytes Can Generate Bona Fide Sall1+ Microglia

Medicine, Neurology, Life Sciences, Cell Biology, Immunology,
monocytes   brain macrophages   fetal liver monocytes   microglia   Alzheimer's disease   cell replacement therapy   epigenetics  

Academic Background The homeostasis of the central nervous system (CNS) relies on two key types of macrophages: microglia and border-associated macrophages (BAMs). Traditionally, microglia are believed to originate from the embryonic yolk sac and possess lifelong self-renewal capabilities, while bone marrow (BM)-derived monocytes in adults cannot r...

Vaccination of Nonhuman Primates Elicits a Broadly Neutralizing Antibody Lineage Targeting a Quaternary Epitope on the HIV-1 Env Trimer

Medicine, Infectious Diseases, Life Sciences, Cell Biology, Biochemistry, Immunology, Microbiology,
Nonhuman Primates   HIV-1 Env Trimer   Broadly Neutralizing Antibodies   Quaternary Epitope   Vaccination  

1. Research Background The envelope glycoprotein (Env) of human immunodeficiency virus type 1 (HIV-1) is the primary target of neutralizing antibodies, but its high variability poses challenges for vaccine development. Broadly neutralizing antibodies (bnAbs) are rare in natural infections and typically require years to emerge. Although Env trimer m...

DDX24 Spatiotemporally Orchestrates VEGF and Wnt Signaling During Developmental Angiogenesis

Medicine, Life Sciences, Cell Biology, Biochemistry, Immunology, Genetics,
angiogenesis   endothelial cells   spatial transcriptomics   VEGF   DDX24  

Research Background Vascular system development is a highly precise regulatory process involving two key stages: vasculogenesis and angiogenesis. Although the VEGF (vascular endothelial growth factor) and Wnt signaling pathways have been confirmed to regulate vascular development in the peripheral and central nervous systems (CNS), respectively, th...