Project Details
Projekt
Reciprocal Modulation of Basophils and B cells in Health and Disease
Subject Area
Pediatric and Adolescent Medicine
Term
from 2012 to 2016
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 232934545
B cells play an important role in the pathogenesis of several diseases, in particular during the development of autoimmunity. In systemic lupus erythematosus, a break in B cell tolerance leads to the production of pathogenic autoantibodies. There is an increasing body of evidence that the interaction between B cells and basophil granulocytes, by direct cell contact or via soluble mediators, plays a role herein. Therefore, the interaction between basophils and B cells will be analysed in the proposed project.In preliminary experiments with co-cultures containing basophils and B cells from healthy individuals, we could demonstrate, that basophils inhibit the differentiation of B cells into plasma cells and the production of antibodies. On the other hand, crosslinking of basophil surface-bound antibodies increased the survival of basophils and their production of the B cell survival factor BAFF.In addition to functional aspects of the interaction between basophils and B cells, it is also aimed to identify the underlying mechanisms. Possible responsible mediators are immunoglobulins, CD40/CD40 ligand, BAFF and cytokines. Especially the role of certain kinases participating in the signal transduction cascades down-stream of the B cell receptor and the Fc epsilon receptor I alpha on basophils will be investigated, since the signalling events of these receptors show remarkable similarities. Recently developed kinase-inhibitors, for example inhibitors of the kinases Btk and syk might therefore affect both basophils and B cells and their interaction and could represent new therapeutical targets for treatment of diseases in which the interaction contributes to pathogenesis. The findings from the co-culture experiments will be directly translated to cells from diseased individuals. It will be investigated if there is evidence for a disturbed interaction between B cells and basophils in patients with systemic lupus erythematodes and the immunodeficiency hyper IgE syndrome. In a previous study with hyper IgE syndrome patients, we demonstrated elevated serum BAFF levels. High levels of IgE binding to basophils, could lead to the activation of basophils and subsequent BAFF production. This will be investigated as a part of the proposed project. In summary, the results of this project will lead to an improved understanding of lupus erythematosus and hyper IgE syndrome and could lead to the discovery of new therapeutic modalities.
DFG Programme
Research Grants
Participating Persons
Professorin Dr. Ellen D. Renner; Professor Dr. Torsten Witte
