B cells and Plasma Cells
as modulators of different immune niches
B cells have a pivotal function in the pathogenesis of autoimmune diseases, such as Systemic Sclerosis (SSc) and primary Sjoegren`s Syndrome (pSS); but also autoimmune intestinal inflammation. B cells thereby orchestrate (auto-)antigen presentation, cytokine production and (auto-)antibody production, the latter via their differentiation into antibody secreting plasmablasts and plasma cells. Our research focusses on how B cells regulate inflammation in different immune niches, such as the skin, adipose tissue and the gut. We use a mouse model of Wiskott-Aldrich Syndrome (WAS), as well as primary human cells isolated from a variety of tissue niches to study the interplay of B cells with other immune cells and the microenvironment during inflammation and autoimmunity.
Current projects in the Keppler lab include:
(1) the role of the actin cytoskeleton in regulating B cell metabolism during TLR-mediated B cell responses;
(2) the influence of aberrant B cell activation and plasma cell formation on immune cell crosstalk in metabolic niches such as the lamina propria of the gut, the adipose tissue, or the skin
(3) the plasticity and function of plasma cells in different immune niches during homeostasis and inflammation.
(4) the pro-fibrotic potential of B cells – directly by interaction with cells (e.g. fibroblasts, macrophages) or indirectly by changing the inflammatory niche.
To address cell-cell and cell-niche interactions, we employ in vitro co-culture systems, state-of-the-art single-cell analysis methods like advanced multi-colour flow cytometry and single-cell RNA sequencing, but also modern imaging techniques like whole organ 3D imaging and image cytometry. We furthermore established collaborations with physicists and microscopists to develop new approaches in order to achieve a more systemic analysis of autoimmune disorders.