Academic Journal
CD21 primes extrafollicular differentiation of autoreactive B cells in a TLR7-driven lupus model.
| Τίτλος: | CD21 primes extrafollicular differentiation of autoreactive B cells in a TLR7-driven lupus model. |
|---|---|
| Συγγραφείς: | Zhu DY; Program in Cellular and Molecular Medicine, Boston Children's Hospital, Harvard Medical School, Boston, USA.; Harvard Graduate Program in Virology, Boston, USA.; Department of Microbiology, Harvard Medical School, Boston, USA., Maurer DP; Harvard Graduate Program in Virology, Boston, USA.; Department of Microbiology, Harvard Medical School, Boston, USA.; Ragon Institute of Mass General, MIT, and Harvard, Cambridge, USA., Castrillon C; Department of Medicine, Emory University School of Medicine, Atlanta, USA., Deng Y; Ragon Institute of Mass General, MIT, and Harvard, Cambridge, USA., Mohamed FAN; Ragon Institute of Mass General, MIT, and Harvard, Cambridge, USA., Ma M; Program in Cellular and Molecular Medicine, Boston Children's Hospital, Harvard Medical School, Boston, USA., Tang D; Pfizer Centers for Therapeutic Innovation, Boston, USA., Min-Debartolo J; Pfizer Centers for Therapeutic Innovation, Boston, USA., Higginson-Scott N; Pfizer Centers for Therapeutic Innovation, Boston, USA., Buhlmann J; Pfizer Centers for Therapeutic Innovation, Boston, USA., Schmidt AG; Department of Microbiology, Harvard Medical School, Boston, USA.; Ragon Institute of Mass General, MIT, and Harvard, Cambridge, USA., Lingwood D; Ragon Institute of Mass General, MIT, and Harvard, Cambridge, USA., Carroll MC; Program in Cellular and Molecular Medicine, Boston Children's Hospital, Harvard Medical School, Boston, USA.; Department of Pediatrics, Harvard Medical School, Boston, USA. |
| Πηγή: | Science immunology [Sci Immunol] 2025 Nov 14; Vol. 10 (113), pp. eads8226. Date of Electronic Publication: 2025 Nov 14. |
| Τύπος έκδοσης: | Journal Article; Research Support, N.I.H., Extramural |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: American Association for the Advancement of Science Country of Publication: United States NLM ID: 101688624 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2470-9468 (Electronic) Linking ISSN: 24709468 NLM ISO Abbreviation: Sci Immunol Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Washington, DC : American Association for the Advancement of Science, [2016]- |
| Ιατρικοί όροι (MeSH): | Toll-Like Receptor 7*/immunology , Lupus Erythematosus, Systemic*/immunology , Receptors, Complement 3d*/immunology , B-Lymphocytes*/immunology , Cell Differentiation*/immunology, Autoantibodies/immunology ; Animals ; Mice ; Disease Models, Animal ; Mice, Inbred C57BL ; Autoimmunity ; Female ; Membrane Glycoproteins |
| Περίληψη: | The extrafollicular (EF) B cell differentiation pathway has emerged as a prominent source of autoantibody-secreting cells (ASCs) in systemic lupus erythematosus (SLE). CD21loCD11c+ B cells are associated with aging, infection, and autoimmunity. They are key contributors to EF ASCs, yet their developmental trajectory and receptor programming are unclear. To study EF mechanics of autoreactive B cells, we adoptively transferred naïve B cell populations into 564Igi mice, which act as an autoreactive host enriched for autoantigens and T cell help. Time-resolved analyses revealed a Toll-like receptor 7 (TLR7)-dependent early escape of peripheral tolerance and a pre-ASC division program. We identified naïve-derived CD21lo cells as precursors of EF ASCs exhibiting elevated reliance on TLR7. Repertoire analysis delineated protoautoreactive B cell selection and receptor evolution toward self-reactivity. Continuous complement receptor 2 (CR2/CD21)-complement C3d and CD21-complement iC3b engagement triggered receptor down-regulation before proliferation. We reveal CD21 as an initiator of TLR7-dependent autoimmune EF proliferation and target for suppressing autoreactivity. |
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| Grant Information: | R01 AI155447 United States AI NIAID NIH HHS; R01 AR074105 United States AR NIAMS NIH HHS; R01 AI146785 United States AI NIAID NIH HHS; R21 AI193280 United States AI NIAID NIH HHS; R01 AI146779 United States AI NIAID NIH HHS; R01 AI130307 United States AI NIAID NIH HHS; R01 AI137057 United States AI NIAID NIH HHS; R01 AI153098 United States AI NIAID NIH HHS; P01 AI089618 United States AI NIAID NIH HHS |
| Substance Nomenclature: | 0 (Toll-Like Receptor 7) 0 (Receptors, Complement 3d) 0 (Tlr7 protein, mouse) 0 (Autoantibodies) 0 (Membrane Glycoproteins) |
| Entry Date(s): | Date Created: 20251114 Date Completed: 20251114 Latest Revision: 20260813 |
| Update Code: | 20261010 |
| PubMed Central ID: | PMC13123569 |
| DOI: | 10.1126/sciimmunol.ads8226 |
| PMID: | 41237221 |
| Βάση Δεδομένων: | MEDLINE |
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