A2: B cells as drivers towards clinical SLE manifestation
Background. SLE is characterized by plasmacytosis-mediated hypergammaglobulinemia and autoantibody production, which lead to glomerulonephritis. In SLE patients and mouse models, autoantibodies are present long before clinical manifestations. Moreover, our data indicate that progression from autoimmunity to disease is accompanied by translocation of autoantibody-producing plasma cells (PCs) from the spleen to the bone marrow and eventually into inflamed kidneys. PC populations include long-lived PCs, which are relatively resistant to immunosuppression (Nat Med. 14:748). We found that during aging and plasmacytosis, PCs are an important source of IL-10, which has immunosuppressive effects, including neutrophil inhibition and promotion of Treg activity (JACI 137:1487; Front Immunol. 10:1183, Fig. A2-1).
Objectives. (i) Provide a comprehensive picture of changes of autoreactive B cell/PC populations during disease progression in murine SLE. (ii) Explore the role of B lineage-derived IL-10 during different stages of SLE development.
Work program. Track the progression and tissue localization of (autoreactive) B cell/PC populations and changes in their antibody isotypes in lupus-prone mice; evaluate the correlations with neutrophil and Treg activity and pathogenesis. For this purpose, IL-10+ cells will be identified by use of IL-10-reporter mice. In the functional studies, IL-10 will be blocked using antibodies at various time points, and its consequences on Treg and neutrophil functions and disease will be investigated. Because disease develops in ageing in lupus-prone mice, adoptive cell transfer from old/diseased to young/healthy lupus-prone mice will be employed to study the impact of B cell populations on disease progression together with A3.
![A2: B cells as drivers towards clinical SLE manifestation A2: B cells as drivers towards clinical SLE manifestation](/fileadmin/_processed_/7/1/csm_uzl_dachfenster_da28f23bf5.jpg)
- Projects
- 1st Generation
- A: Defining Autoimmune Pre-Disease
- A1: Define the impact of shift work on autoimmunity and autoimmune diseases
- A2: B cells as drivers towards clinical SLE manifestation
- A3: G protein-coupled receptors orchestrating granulocytes in pemphigoid diseases
- A4: Epitope-dependent autoantibody-mediated skin inflammation in pemphigoid disease
- A5: Chronic danger signaling as driver of autoimmunity in granulomatosis with polyangiitis
- A6: T cell memory differentiation in early autoimmune disease
- A7: CD4+ T cell receptor sequences during progression towards experimental pemphigoid.
- A8: The C5aR2 pathway as a checkpoint for B cell activation in autoimmunity.
- A9: Genetic and molecular similarity of autoimmune disease
- B: Targeting of Autoimmune Pre-Disease
- Associated projects
- MD projects
- Concluded Projects
- A: Defining Autoimmune Pre-Disease
- 2nd Generation
- 1st Generation