Daria Martin, Schering Stiftung Projektraum

 

Avrion Mitchison Prize 2013

Dirk Baumjohann, PhD is the recipient of the 2013 Avrion Mitchison Prize for Rheumatology for his work “Persistent antigen and germinal center B cells sustain T follicular helper cell responses and phenotype”.

Baumjohann grew up in Germany and did his undergraduate studies in Molecular Medicine at the University of Erlangen. After an internship in Uli von Andrian's lab at Harvard Medical School, he went to Switzerland to work on his PhD research with Federica Sallusto and Antonio Lanzavecchia at the Institute for Research in Biomedicine and received his PhD degree in Immunology/Cell Biology from the University of Bern. In Mark's lab at UCSF he is now working on the molecular requirements for CD4+ T helper cell differentiation.

At the award ceremony, Dirk Baumjohann will present his current research “Persistent antigen and germinal center B cells sustain T follicular helper cell responses and phenotype”:

„T helper (Th) cells orchestrate cellular and humoral (antibody-mediated) immune responses against a variety of pathogens. In recent years, T follicular helper (TFH) cells have emerged as the prototypic Th cell subset that provides help to B cells. In this regard, TFH cells are crucial for the establishment of germinal centers (GCs), in which the processes of somatic hypermutation, affinity maturation, and class switch recombination lead to the generation of memory B cells and long-lived plasma cells that produce high-affinity antibodies. Due to their central role in controlling humoral immunity, dysregulated TFH cells can contribute to the development of autoimmunity and allergies. Accordingly, several autoimmune diseases are characterized by increased TFH cell numbers and by the production of autoantibodies, including rheumatoid arthritis and systemic lupus erythematosus.

We could demonstrate that the magnitude of the TFH cell and GC B cell response was dictated by the amount of antigen and that TFH cell numbers directly correlated with the extent of the GC B cell response. Previous work established that the initiation of the TFH cell program occurs during priming by dendritic cells, independent of cognate interactions with B cells. Nevertheless, B cells play an important role for TFH cells at later stages during the GC response, as B cells become the sole antigen-presenting cell type for TFH cells. Therefore, we next aimed at defining the requirements for the maintenance of TFH cells. Through the combined use of adoptive transfer approaches, in vivo blocking antibody treatments, and diphtheria toxin-mediated depletion of GC B cells in carefully controlled bone marrow chimera experiments, we revealed that maintenance of TFH cells required sustained antigenic stimulation and interaction with GC B cells. Retransfer of TFH cells to naïve mice resulted in a rapid loss of the TFH cell phenotype. While depletion of non-GC B cells during the peak of the GC response did not affect TFH and GC B cell numbers, interference with cognate interactions between TFH and GC B cells by blockade of ICOS/ICOSL or CD40/CD40L pathways rapidly resulted in the dissolution of the GC response.

Another important finding was that immunization under T cell-lymphopenic conditions generated dysregulated TFH cells, leading to hypergammaglobulinemia and autoantibody production. These data indicate that dysregulated TFH cell responses might contribute to the pathology of diseases that are characterized by T cell lymphopenia, such as HIV infection and certain tumors. Taken together, the results of this study have important implications for our current understanding of T cell-B cell interactions and may help uncovering novel avenues for therapeutic intervention in autoimmune diseases or for boosting the immune response in vaccine settings.”

 

Award Ceremony on December 3, 2013, at 5:00 p.m.


The Avrion Mitchison Prize, which is funded by the Ernst Schering Foundation, is presented in conjunction with the Albrecht Hasinger Lecture at the German Rheumatism Research Center (DRFZ).

Foyer of the German Rheumatism Research Center Berlin
Charité Mitte Campus
Charitéplatz 1
10117 Berlin
www.drfz.de

 

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