Centrum für Chronische Immundefizienz - CCI

Research focus

Development and homeostasis of human B cells.

Current Projects

BAFF-regulated B cell survival and differentiation

B precursor cells develop in the bone marrow into IgM-positive immature B cells. These cells then migrate through the blood stream into the spleen where they differentiate into follicular and marginal zone B cells (Figure 1).

Figure 1. A. Expression of BAFFR. TACI and BCMA in B cell development.
Critical developmental steps depending on BAFF and APRIL- induced signals are shown by the presence of the respective ligand. B. Immunofluorescence of human spleen showing a large germinal center surrounded by follicular and marginal zone B cells. (from Front. Immunol., 08 October 2018 | https://doi.org/10.3389/fimmu.2018.02285)

During this last step of B cell development, these cells receive pro-survival signals through the TNF-like cytokine BAFF (B cell activation factor of the TNF-family), which binds to its receptor termed BAFFR. BAFF-BAFFR binding increases the metabolic fitness of the cells by enhancing protein synthesis and mitochondrial activity. BAFF can also bind to a related receptor termed TACI, which is expressed by marginal zone B cells and class-switched memory B cells. In addition to BAFF; TACI can also bind another BAFF-like ligand, which is called APRIL. Activation of TACI enhances immunoglobulin-class switch and the formation of plasma cells in T-independent immune responses (Figure 2). It also acts as decoy receptor for BAFF and APRIL thereby limiting the bioavailability of both ligands.

Figure 2. BAFF and BAFF receptors.
BAFF binds to BAFFR, TACI and BCMA while APRIl only binds TACI and BCMA. BAFFR is expressed by all B cell subpopulations except plasma cells, TACI by marginal zone B cells, switche memory B cells and plasma cells, and BCMA by plasma cells. All three receptors regulate the survival of the different subpopulations.

We are investigating in the interactions between BAFFR, TACI and other proteins expressed by B cells as well as in the different intracellular signaling pathways and physiological responses which are regulated by BAFF binding to BAFFR and TACI. To this end, we have established in vitro assay and differentiation systems for human B cells, gene transfer and gene targeting approaches as well as various ways to study protein functions and interactions including FRET, immunoprecipitations, live microscopy and flow cytometry.

Funding and Collaborations

We are funded by the DFG within the comprehensive research center TRR130 "B cells in immunity and autoimmunity" which combines 25 research groups from Erlangen, Ulm Freiburg, Göttingen and Berlin. We are also funded by the e-rare program together with research groups from Milano, Paris, Ghent and Dresden within the project "EDSCIDPROG".

http://www.trr130.forschung.uni-erlangen.de/index.php/de/home.html
http://www.trr130.forschung.uni-erlangen.de/index.php/en/id-06-hermann-eibel.html
http://www.erare.eu/financed-projects/edscidprog

Publications

A list of publications can be found on PubMed:

https://www.ncbi.nlm.nih.gov/pubmed/?term=eibel+h 

Team

CV Hermann Eibel