

Other version: http://www.jimmunol.org/cgi/reprint/177/4/2285.pdf
![]() |
The Th2 lymphoproliferation developing in LatY136F mutant mice triggers polyclonal B cell activation and systemic autoimmunity |
|
Authors | ||
Published in | The Journal of immunology. 2006, vol. 177, no. 4, p. 2285-2293 | |
Abstract | Lat(Y136F) knock-in mice harbor a point mutation in Tyr(136) 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 Lat(Y136F) 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 Lat(Y136F) mice revealed the presence of a previously uncharacterized CD93-expressing subpopulation, whose presence was confirmed in wild-type mice after immunization. In Lat(Y136F) 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 Lat(Y136F) serum, we observed early-onset systemic autoimmunity with nephritis showing IgE autoantibody deposits and severe proteinuria. These results show that Th2 cells developing in Lat(Y136F) mice can trigger polyclonal B cell activation and thereby lead to systemic autoimmune disease. | |
Keywords | Adaptor Proteins, Signal Transducing/genetics/*physiology — *Amino Acid Substitution/genetics — Animals — Autoimmune Diseases/*genetics/*immunology/pathology — B-Lymphocytes/cytology/*immunology/pathology — Clone Cells — Lymphocyte Activation/*genetics — Lymphoproliferative Disorders/*genetics/immunology — Membrane Proteins/genetics/*physiology — Mice — Mice, Inbred C57BL — Mice, Knockout — Mice, Mutant Strains — Phenylalanine/genetics — Phosphoproteins/genetics/*physiology — Th2 Cells/immunology/*pathology — Tyrosine/genetics | |
Identifiers | PMID: 16887989 | |
Full text | ||
Citation (ISO format) | GENTON, Celine et al. The Th2 lymphoproliferation developing in LatY136F mutant mice triggers polyclonal B cell activation and systemic autoimmunity. In: The Journal of immunology, 2006, vol. 177, n° 4, p. 2285-2293. doi: 10.4049/jimmunol.177.4.2285 https://archive-ouverte.unige.ch/unige:11273 |