“Primary and Secondary B Cell Activation”, Jürgen Wienands, Georg August University Göttingen, Germany

Speaker: Prof. Dr. Jürgen Wienands , Georg August University Göttingen, Germany

Host: Dr. John Lindner, BioMed X

Abstract

The B cell antigen receptor (BCR) plays a key role for antibody-mediated humoral immune responses. The general BCR structure comprises a membrane-bound immunoglobulin molecule of any of the five known isotypes (i.e. IgM, IgD, IgG, IgA or IgE) in association with the canonical signaling components CD79a and CD79b.

The group investigates the mechanics of proximal and distal BCR signaling events and what distinguishes primary activation of newly generated B cells from recall responses of memory B cells.

The seminar will focus on the identification of intracellular BCR effector proteins and their mode of action as well as on BCR isotype-specific signal signatures promoting the recognition of antigens with heightened sensitivity and hence the vigorous responsiveness of memory B cells.

About Jürgen

since 2004: Full Professor for “Molecular and Cellular Immunology” at the University of Göttingen
2001- 2004: Full Professor for “Biochemistry and Molecular Immunology” at the University of Bielefeld
2001: “Habilitation” and Venia Legendi in “Molecular Immunology and Biochemistry”
1996- 2001: Group leader at the University of Freiburg, Institute of Biology III

Major Research Interests
The signature structure of B lymphocytes is their clonotypic antigen receptor (BCR), which recognizes extracellular pathogens or toxins, and consequently initiates their combating by soluble antibodies.

Our research focuses on how the ligated BCR activates intracellular signaling pathways upon primary and secondary antigen encounter. Our studies showed that BCR classes expressed on antigen-experienced, so-called memory B cells, possess a signal amplification mechanism that lowers the BCR signaling threshold compared to newly generated B cells. This finding provides a molecular explanation for immunological memory which is the fundamental basis for successful vaccination strategies.

We also identified key effector proteins of the BCR such as SLP-65 or CIN85. They function as adaptor proteins which nucleate the formation of multi-molecular protein complexes to integrate and amplify BCR signals. Interference with expression or function of these effectors cause severe immunodeficiencies in mouse and man.

To investigate these processes we apply cutting edge technologies of biochemistry and genetics including protein interaction studies, flow cytometry, targeted gene disruption in cell culture and embryonic stem cells followed by reconstitution experiments using electroporation techniques or retroviral gene transfer.

Homepage Department/Research Group

Selected Recent Publications

  • Keller B, Shoukier M, Schulz K, Bhatt A, Heine I, Strohmeier V, Speckmann C, Engels N, Warnatz K, Wienands J (2018) Germline deletion of CIN85 in humans with X chromosome-linked antibody deficiency. J Exp Med. 215(5): 1327-1336
  • Kühn J, Wong LE, Pirkuliyeva S, Schulz K, Schwiegk C, Fünfgeld KG, Keppler S, Batista FD, Urlaub H, Habeck M, Becker S, Griesinger C, Wienands J (2016) The adaptor protein CIN85 assembles intracellular signaling clusters for B cell activation. Sci Signal 9(434): ra66
  • Lutz J, Dittmann K, Bösl MR, Winkler TH, Wienands J, Engels N (2015) Reactivation of IgG-switched memory B cells by BCR-intrinsic signal amplification promotes IgG antibody production. Nat Commun 6: 8575
  • Engels N, König LM, Schulze W, Radtke D, Vanshylla K, Lutz J, Winkler TH, Nitschke L, Wienands J (2014) The immunoglobulin tail tyrosine motif upgrades memory-type BCRs by incorporating a Grb2-Btk signalling module. Nat Commun 5: 5456for review see:
  • Wienands J, Engels N (2016) The Memory Function of the B Cell Antigen Receptor. Curr Top Microbiol Immunol 393: 107-21