- Authors:
-
Hua, Z; Gross, Aj; Lamagna, C; Ramos Hernández, N; Scapini, Patrizia; Ji, M; Shao, H; Lowell, Ca; Hou, B; Defranco, Al
- Title:
-
Requirement for MyD88 Signaling in B Cells and Dendritic Cells for Germinal Center Anti-Nuclear Antibody Production in Lyn-Deficient Mice.
- Year:
-
2014
- Type of item:
-
Articolo in Rivista
- Tipologia ANVUR:
- Articolo su rivista
- Language:
-
Inglese
- Referee:
-
Sì
- Name of journal:
- Journal of Immunology
- ISSN of journal:
- 0022-1767
- N° Volume:
-
192
- Number or Folder:
-
3
- Page numbers:
-
875-885
- Keyword:
-
immunology; Myd88; B cells; myeloid cells; Lyn(-/-) mice; lupus erythematosus
- Short description of contents:
- The intracellular tyrosine kinase Lyn mediates inhibitory receptor function in B cells and myeloid cells, and Lyn(-/-) mice spontaneously develop an autoimmune and inflammatory disease that closely resembles human systemic lupus erythematosus. TLR-signaling pathways have been implicated in the production of anti-nuclear Abs in systemic lupus erythematosus and mouse models of it. We used a conditional allele of Myd88 to determine whether the autoimmunity of Lyn(-/-) mice is dependent on TLR/MyD88 signaling in B cells and/or in dendritic cells (DCs). The production of IgG anti-nuclear Abs, as well as the deposition of these Abs in the glomeruli of the kidneys, leading to glomerulonephritis in Lyn(-/-) mice, were completely abolished by selective deletion of Myd88 in B cells, and autoantibody production and glomerulonephritis were delayed or decreased by deletion of Myd88 in DCs. The reduced autoantibody production in mice lacking MyD88 in B cells or DCs was accompanied by a dramatic decrease in the spontaneous germinal center (GC) response, suggesting that autoantibodies in Lyn(-/-) mice may depend on GC responses. Consistent with this view, IgG anti-nuclear Abs were absent if T cells were deleted (TCRβ(-/-) TCRδ(-/-) mice) or if T cells were unable to contribute to GC responses as the result of mutation of the adaptor molecule SAP. Thus, the autoimmunity of Lyn(-/-) mice was dependent on T cells and on TLR/MyD88 signaling in B cells and in DCs, supporting a model in which DC hyperactivity combines with defects in tolerance in B cells to lead to a T cell-dependent systemic autoimmunity in Lyn(-/-) mice.
- Product ID:
-
79849
- Handle IRIS:
-
11562/670158
- Deposited On:
-
February 21, 2014
- Last Modified:
-
November 11, 2022
- Bibliographic citation:
-
Hua, Z; Gross, Aj; Lamagna, C; Ramos Hernández, N; Scapini, Patrizia; Ji, M; Shao, H; Lowell, Ca; Hou, B; Defranco, Al,
Requirement for MyD88 Signaling in B Cells and Dendritic Cells for Germinal Center Anti-Nuclear Antibody Production in Lyn-Deficient Mice.
«Journal of Immunology»
, vol.
192
, n.
3
,
2014
,
pp. 875-885
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