TY  - THES
AB  - B lymphocytes and dendritic cells (DC) internalize, process, and present antigens as peptide:MHC complexes to T lymphocytes. In case of B lymphocytes the antigen recognition occurs specifically via the B cell antigen receptor (BCR). Concomitantly, BCR-mediated signaling cascades are initiated with the participation of different effector or adaptor proteins. Two adaptor proteins that provide this signaling are mAbp1 and HS1.
In the present work I could show for the first time a direct interaction of mAbp1 and HS1 in murine B lymphocytes via immune precipitation experiments. In comparison to wt cells, primary cells deficient in mAbp1 and/or HS1 exhibited a reinforced BCR-mediated overall protein tyrosine phosphorylation. Moreover, they showed reduced Ca2+ mobilization from stores of the endoplasmic reticulum and an increased Ca2+ flux across the plasma membrane.
The Ca2+ phenotype could be due to an interaction between mAbp1 or HS1 and proteins controlling Ca2+ mobilization. Indeed, I could show an association between HS1 and the SH2 domain of SLP-65, which is an essential, positive Ca2+-regulatory element of BCR-mediated signaling. In addition, an interaction between HS1 and the negative-regulatory inositol phosphatase SHIP after BCR stimulation could be demonstrated.
Using mAbp1-deficient mice as detection tool a B220low/-/CD19low/-/IgG+ cell population with memory B cell character could be identified via flow cytometry. The population showed a fivefold increased IgG expression in comparison to wt control. In mAbp1/HS1-double-deficient animals this population was not detectable.
Analyzing mAbp1-deficient DC a reduced antigen endocytosis rate and diminished expression of co-stimulatory proteins could be shown. The DC-mediated activation of CD4+ T cells in vitro was drastically enhanced in comparison to wt control.
In summary, the results show that mAbp1 and HS1 orchestrate both positive- and negative-regulatory molecules and thereby controlling the kinetic of antigen-induced, BCR-proximal signaling. Furthermore the antigen-dependent differentiation and the composition of B cell populations with memory character are decisively influenced by mAbp1 and HS1. In DC the adaptor protein mAbp1 possesses a positive-regulatory function during antigen internalization and expression of co-stimulatory molecules and inhibits DC-mediated activation of CD4+ T cells. The present work demonstrates a pivotal role of the adaptor proteins mAbp1 and HS1 in the initiation and maintenance of the humoral immune response in B lymphocytes and DC.
DA  - 2010
KW  - B-Lymphocyten
KW  - Dendritische Zellen
KW  - B-Zell-Antigenrezeptor
KW  - Adaptorproteine
KW  - HS1
KW  - mAbp1
KW  - Adaptor proteins
KW  - B cell antigen receptor
KW  - Dendritic cells
KW  - B lymphocytes
KW  - Signaltransduktion
LA  - ger
PY  - 2010
TI  - Integration der Adapterproteine mAbp1 und HS1 in signalleitende Prozesse von B-Lymphocyten und dendritischen Zellen
UR  - https://nbn-resolving.org/urn:nbn:de:hbz:361-16892
Y2  - 2024-11-22T06:49:31
ER  -