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Epstein-Barr virus-driven cardiolipin synthesis sustains metabolic remodeling during B cell transformation.
Sci Adv
January 2025
Department of Molecular Biology and Microbiology, Tufts University, Boston, MA 02111, USA.
The Epstein-Barr virus (EBV) infects nearly 90% of adults globally and is linked to over 200,000 annual cancer cases. Immunocompromised individuals from conditions such as primary immune disorders, HIV, or posttransplant immunosuppressive therapies are particularly vulnerable because of EBV's transformative capability. EBV remodels B cell metabolism to support energy, biosynthetic precursors, and redox equivalents necessary for transformation.
View Article and Find Full Text PDFUnveiling inverted D genes and D-D fusions in human antibody repertoires unlocks novel antibody diversity.
Commun Biol
January 2025
Large Molecules Research, Sanofi, Cambridge, MA, USA.
Antibodies, essential components of adaptive immunity, derive their remarkable diversity primarily from V(D)J gene rearrangements, particularly within the heavy chain complementarity-determining region 3 (CDR-H3) where D genes play a major role. Traditionally, D genes were thought to recombine only in the forward direction, despite having identical recombination signal sequences (12 base pair spacers) at both ends. This observation led us to question whether these symmetrical sequences might enable bidirectional recombination.
View Article and Find Full Text PDFAntigen receptor ITAMs provide tonic signaling by acting as guanine nucleotide exchange factors to directly activate R-RAS2.
Sci Signal
January 2025
Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas, Universidad Autónoma de Madrid, 28049 Madrid, Spain.
The small GTPase R-RAS2 regulates homeostatic proliferation and survival of T and B lymphocytes and, when present in high amounts, drives the development of B cell chronic lymphocytic leukemia. In normal and leukemic lymphocytes, R-RAS2 constitutively binds to antigen receptors through their immunoreceptor tyrosine-based activation motifs (ITAMs) and promotes tonic activation of the phosphatidylinositol 3-kinase (PI3K) signaling pathway. Here, we examined the molecular mechanisms underlying this direct interaction and its consequences for R-RAS2 activity.
View Article and Find Full Text PDFIL-21 signaling promotes IgM B cell proliferation and antibody production via JAK/STAT3 and AKT pathways in early vertebrates.
Dev Comp Immunol
January 2025
Institute of Modern Aquaculture Science and Engineering, School of Life Sciences, South China Normal University, Guangzhou, 510631, China; Guangzhou Key Laboratory of Subtropical Biodiversity and Biomonitoring, Guangdong Provincial Engineering Technology Research Center for Environmentally-Friendly Aquaculture, South China Normal University, Guangzhou, 510631, China. Electronic address:
IL-21 is a type I cytokine that is produced by activated CD4 T cells and has a significant impact on the growth, survival, and functional activation of B lymphocytes. While IL-21 has been identified in several teleost fish species, its function and associated mechanisms focus on teleost fish B cells remain largely unknown. In this study, we aimed to investigate the effects of IL-21 (OnIL-21) on IgM B cells from Nile tilapia (Oreochromis niloticus), as well as the intracellular signaling transduction pathway involved.
View Article and Find Full Text PDFIntercellular Epigenomic Signalling via Extracellular Vesicles During B Cell Maturation.
J Extracell Vesicles
January 2025
Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland.
B cell maturation is crucial for effective adaptive immunity. It requires a complex signalling network to mediate antibody diversification through mutagenesis. B cells also rely on queues from other cells within the germinal centre.
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