The Th2 Lymphoproliferation Developing in Lat Y136F Mutant Mice Triggers Polyclonal B Cell Activation and Systemic Autoimmunity
| Autor: | Ying Wang, Bernard Malissen, Marie Malissen, Georges Delsol, Shozo Izui, Hans Acha-Orbea, Céline Genton, Gilbert J. Fournié |
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| Přispěvatelé: | Centre d'Immunologie de Marseille - Luminy (CIML), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Haon, Marie Laure |
| Rok vydání: | 2006 |
| Předmět: |
Adoptive cell transfer
MESH: Mice Mutant Strains ddc:616.07 Plasma cell Lymphocyte Activation MESH: Mice Knockout MESH: Tyrosine Autoimmune Diseases/*genetics/*immunology/pathology Mice MESH: Lymphoproliferative Disorders 0302 clinical medicine MESH: Autoimmune Diseases Lymphoproliferative Disorders/*genetics/immunology Immunology and Allergy MESH: Animals Memory B cell Mice Knockout B-Lymphocytes 0303 health sciences Th2 Cells/immunology/*pathology Membrane Proteins/genetics/*physiology MESH: Amino Acid Substitution 3. Good health Adaptor Proteins Signal Transducing/genetics/*physiology medicine.anatomical_structure [SDV.IMM]Life Sciences [q-bio]/Immunology MESH: Membrane Proteins [SDV.IMM] Life Sciences [q-bio]/Immunology Phenylalanine T cell Immunology Naive B cell Linker for Activation of T cells Biology MESH: Phosphoproteins Autoimmune Diseases Phenylalanine/genetics MESH: Phenylalanine 03 medical and health sciences Th2 Cells MESH: Mice Inbred C57BL MESH: Th2 Cells MESH: B-Lymphocytes medicine Animals B-Lymphocytes/cytology/*immunology/pathology MESH: Lymphocyte Activation Lymphocyte Activation/*genetics MESH: Mice Phosphoproteins/genetics/*physiology B cell Adaptor Proteins Signal Transducing Tyrosine/genetics MESH: Adaptor Proteins Signal Transducing 030304 developmental biology MESH: Clone Cells Membrane Proteins Germinal center Phosphoproteins Lymphoproliferative Disorders Mice Mutant Strains Amino Acid Substitution/genetics Clone Cells Mice Inbred C57BL Amino Acid Substitution Tyrosine 030215 immunology |
| Zdroj: | Journal of Immunology Journal of Immunology, 2006, 177 (4), pp.2285-93 Journal of Immunology, Vol. 177, No 4 (2006) pp. 2285-2293 Journal of Immunology, Publisher : Baltimore : Williams & Wilkins, c1950-. Latest Publisher : Bethesda, MD : American Association of Immunologists, 2006, 177 (4), pp.2285-93 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.177.4.2285 |
| Popis: | Lat Y136F knock-in mice harbor a point mutation in Tyr136 of the linker for activation of T cells and show accumulation of Th2 effector cells and IgG1 and IgE hypergammaglobulinemia. B cell activation is not a direct effect of the mutation on B cells since in the absence of T cells, mutant B cells do not show an activated phenotype. After adoptive transfer of linker for activation of T cell mutant T cells into wild-type, T cell-deficient recipients, recipient B cells become activated. We show in vivo and in vitro that the LatY136F mutation promotes T cell-dependent B cell activation leading to germinal center, memory, and plasma cell formation even in an MHC class II-independent manner. All the plasma and memory B cell populations found in physiological T cell-dependent B cell responses are found. Characterization of the abundant plasmablasts found in secondary lymphoid organs of LatY136F mice revealed the presence of a previously uncharacterized CD93-expressing subpopulation, whose presence was confirmed in wild-type mice after immunization. In LatY136F mice, B cell activation was polyclonal and not Ag-driven because the increase in serum IgG1 and IgE concentrations involved Abs and autoantibodies with different specificities equally. Although the noncomplement-fixing IgG1 and IgE are the only isotypes significantly increased in LatY136F serum, we observed early-onset systemic autoimmunity with nephritis showing IgE autoantibody deposits and severe proteinuria. These results show that Th2 cells developing in LatY136F mice can trigger polyclonal B cell activation and thereby lead to systemic autoimmune disease. |
| Databáze: | OpenAIRE |
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