Article Text

Download PDFPDF

P03.16 Functional defects in B-cells of patients with von-Hippel-Lindau Syndrome
  1. S Theurich1,
  2. HJ Becker2,
  3. K Wennhold3,
  4. H Schlösser3,
  5. F Marbach3,
  6. M Garcia-Marquez3,
  7. A Shimabukuro-Vornhagen3,
  8. J Schreml3 and
  9. M von Bergwelt-Baildon1
  1. 1LMU Munich, Munich, Germany
  2. 2University of Tokio, Tokio, Japan
  3. 3University Hospital Cologne, Cologne, Germany


Von-Hippel-Lindau (VHL)-disease is an inherited cancer syndrome characterized by a variety of benign and malignant tumors, which develop upon mutation of the second allele of the VHL-tumor suppressor gene. The VHL-protein (pVHL) regulates hypoxia-induced transcription factors (Hif) and by this plays a central role for metabolic cellular adaptations to hypoxic conditions. VHL/Hif regulation plays a well-established role in the development and function of immune cells and already VHL-haploinsufficiency can alter gene expression patterns. In contrast, little is known about primary immune cell functions in VHL-patients. In this study, we analyzed the functional capacity of CD40-stimulated B-cells to act as antigen-presenting cells. We confirmed mono-allelic VHL-gene mutations in B-cells from thirteen VHL-patients and found that their response to CD40-stimulation was significantly reduced. On a functional level this translated to an impaired ability to act as antigen presenting cells leading to impaired T-cell responses in vitro. Taken together, we demonstrate that VHL-haploinsufficiency deregulates B-cell functions following CD40-activation as a new aspect of VHL-syndrome. (The study was registered in the German Clinical Trial Registry (; ID: DRKS00012413).

Disclosure Information S. Theurich: B. Research Grant (principal investigator, collaborator or consultant and pending grants as well as grants already received); Modest; Verein VHL (von Hippel-Lindau) betroffener Familien e.V.. H.J. Becker: None. K. Wennhold: None. H. Schlösser: None. F. Marbach: None. M. Garcia-Marquez: None. A. Shimabukuro-Vornhagen: None. J. Schreml: None. M. von Bergwelt-Baildon: None.

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.