Gegenseitige Beeinflussung zwischen Basophilen und B-Zellen unter physiologischen und pathologischen Konditionen
Zusammenfassung der Projektergebnisse
Basophils are not only important mediators during IgE-related helminth infections and allergy, but also play a role in modulating the function of cells during other immunological reactions. They can be activated by cytokines, chemokines and Toll-like receptor ligands and respond in an antigen-specific manner by means of surface Fc-receptor-bound IgE and IgG. Here, we report that human basophils enhance the maturation of B cells intoplasma cells (PC) by directing B cell class switch recombination towards IgG. Furthermore, the production of IgM, IgA and IgG was enhanced. Thesurface proteins, CD23 and CD40, important for the development of B cells intoPC, were upregulated on B cells in the presence of basophils. These processes depended mainly on basophil-derived IL-4. Also other basophil mediators, histamine, B cell activating factor of the TNF family (BAFF), and IL-3, enhanced the B cell function. Interestingly, IL-3 was a very potent enhancer of in vitro PC development. Because of these results, the phenotype and function of basophils from patients with the autoimmune diseases hyper IgE syndrome (HIES) and systemic lupus erythematosus (SLE) were investigated by flow cytometry and compared with basophils from healthy individuals. The number of samples from HIES patientswas too low to drawstrong conclusions about the phenotype and function of these basophils. SLE basophils expressed ex vivohigher levels of the activation markers CD203c and CD62L, but not of the degranulation marker CD63. Furthermore, they expressed lower levels of the FcεRIα and higher levels of the inhibitory receptor CD32B; although the levels of surface bound IgE and IgG were comparable. Functionally, SLE basophils reacted stronger to activation via the FcεRIα and this was both caused by an as yet unknown serum factor as well as by an intrinsic difference as compared to healthy basophils. Healthy basophils were not affected in their activation ability by the SLE serum factor. Therefore, the signal transduction route following FcεRIα activation (which is similar to the signaling following B cell receptor activation) was investigated. The phosphorylation of Syk was diminished in SLE basophils as compared to healthy basophils. This could be caused by lower levels of Lyn in SLE basophils, which was already observed by others in B cells from SLE patients. Lower Lyn levels lead to the activation of other signaling routes, which cause a higher net cellular activation in B cells. Whether this holds true for basophils needs further investigation. Taken together, basophils are important supporters for B cells, by enhancing their differentiation into PC and antibody production. A higher activation status of basophils would lead to an enhancement of their mediator production which further amplifies PC development. Further investigations are ongoing and are needed in order to estimate if therapeutic approaches can be developed based on our results.
Projektbezogene Publikationen (Auswahl)
- 2013. Human Basophils enhance B cell Proliferation and Survival and Modulate Antibody Production. Abstract for the German Rheumatology Foundation, Heidelberg, Gernmany
Dijkstra D, Meyer-Bahlburg A
- 2013. Human Basophils enhance B cell Proliferation and Survival and Modulate Antibody Production. Abstract for the internal meeting of the Pediatric Research Center of the Hannover medical School, Hannover, Germany
Dijkstra D, Meyer-Bahlburg A
- 2013. Human Basophils enhance B cell Proliferation and Survival and Modulate Antibody Production. Abstract for the International Mast Cell and Basophil Meeting, Udine, Italy
Dijkstra D, Meyer-Bahlburg A
- 2014. Human Basophils enhance B cell Proliferation and Survival and Modulate Antibody Production. Abstract for the International Mast Cell and Basophil Meeting, Munich, Germany
Dijkstra D, Meyer-Bahlburg A
- 2016. Basophile Granulozyten und Autoimmunerkrankungen. Zeitschrift für Rheumatologie 75:245-252
Meyer-Bahlburg M, Dijkstra D
(Siehe online unter https://doi.org/10.1007/s00393-015-0039-1)
