Division of B Cell Immunology

Prof. Dr. Hedda Wardemann

Qualitative assessment of a recombinant antibody (mAB) cloned from a primary human B cell to recognize sporozoites of the malaria parasite Plasmodium falciparum (Pf) (top) and to inhibit Pf traversal of human liver cells (bottom).
© dkfz.de

Antibodies are soluble B cell antigen receptors that efficiently helps the immune system to combat invading pathogens. The majority of available vaccines rely on the induction of highly specific antibody responses. Antibodies are also widely used as biological therapeutics in the treatment of non-infectious diseases, including cancer. However, not all natural antibody responses are protective, and numerous attempts to develop antibody-based vaccines or therapies have been unsuccessful. Due to the enormous diversity of the B cell repertoire, antibody responses can be generated against nearly any structure, but our understanding of the cellular and molecular mechanisms underlying the induction of protective vs. non-protective antibody responses is still limited. The Division of B Cell Immunology studies antibody responses in health and disease. Direct measurements of the composition of the antigen receptor repertoire have long been limited due to the high degree of antibody gene diversity. In order to be able to perform in-depth analyses of the antibody repertoire, we have developed a platform for the high-throughput amplification and sequencing of antibody genes from single cells. The approach is fully compatible with the direct cloning and generation of recombinant monoclonal antibodies. The lab combines experimental tools and bioinformatics to perform molecular and functional analyses of antibody repertoires at the single cell level in mice and humans.

FUTURE OUTLOOK
The B Cell Immunology Department studies the clonal evolution of B cell responses to controlled infection and vaccination in humans and murine animal models, respectively. The long-term goal of the Division is to determine how differences in the antibody repertoire are associated with protective vs. nonprotective antibody responses. Specifically, the research aims at (I) understanding how the antibody repertoire is shaped on a molecular and functional level by antigen-driven selection, (II) defining qualitative differences in the antibody repertoire in health and disease, (III) identifying protective antibodies and exploring their therapeutic potential in cancer and infectious diseases and at (IV) developing strategies for the targeted manipulation of the B cell system in order to induce protective antibody responses.

Contact

Prof. Dr. Hedda Wardemann
B Cell Immunology (D130)
Deutsches Krebsforschungszentrum
Im Neuenheimer Feld 280
69120 Heidelberg
Tel: +49 6221 42 1270

Selected Publications

  • Benckert J, Schmolka N, Kreschel C, Zoller MJ, Sturm A, Wiedenmann B, Wardemann H. (2011). The majority of intestinal IgA+ and IgG+ plasmablasts in the human gut are antigen-specific. J. Clin. Invest. 121(5):1946-55
  • Muellenbeck MF, Ueberheide B, Amulic B, Epp A, Fenyo D, Busse CE, Esen M, Theisen M, Mordmüller B, Wardemann H. (2013). Atypical and classical memory B cells produce Plasmodium falciparum neutralizing antibodies. J. Exp. Med. 210(2):389-99
  • Imkeller K. et al. (2016). sciReptor: Analysis of single-cell level immunoglobulin repertoires. BMC Bioinformatics, 4, 17:67.
  • Murugan R. et al. (2015). Direct high-throughput amplification and sequencing of immunoglobulin genes from single human B cells. Eur J Immunol, 45, 2698-700.
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