A common SNP in BAFF-R impairs receptor multimerization, predisposes to immunodeficiency but reduces the risk to develop chronic lymphocytic leukemia:
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| Main Author: | |
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| Format: | Thesis Book |
| Language: | English |
| Published: |
2013
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| Subjects: | |
| Online Access: | Inhaltsverzeichnis |
| Item Description: | Enth. 1 Zeitschriftenartikel aus J Allergy Clin immunol 2013 |
| Physical Description: | 97, 13 Bl. Ill., graph. Darst. |
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Record in the Search Index
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|---|---|
| adam_text | INDEX
INDEX
SUMMARY 1
ZUSAMMENFASSU
NG 2
1 INTRODUCTION 3
1.1 B CELL DEVELOPMENT IN THE BONE MARROW (BM) 4
1.2 B CELL GUIDANCE TO SECONDARY LYMPHOID ORGANS 5
1.3 FOLLICULAR B CELLS, GERMINAL CENTER REACTION AND HUMORAL MEMORY 6
1.4 MARGINAL ZONE B CELLS 9
1.5 HUMAN B CELL SUBSETS AND THEIR PHENOTYPIC CHARACTERIZATION 10
1.6 THE BAFF SYSTEM 10
1.6.1 THE PHYSIOLOGICAL ROLE OF THE BAFF SYSTEM IN B CELL SURVIVAL 11
1.6.2 BAFF-R SIGNALING 12
1.6.3 BAFF IN B CELL TOLERANCE 14
1.6.4 BAFF IN DISEASES 15
1.6.5 BAFF-R AND BAFF - A BIOCHEMICAL POINT OF VIEW 19
1.6.6 BAFF-R MUTATIONS 21
1.7 THE AIMS OF MY THESIS 22
2 RESULTS
23
2.1 P21R DECREASES THE NUMBER OF FUNCTIONAL BAFF-BINDING SITES 23
2.2 P21R REDUCES BAFF-R MULTIMERIZATION 26
2.3 P21R DOES NOT ALTER LATERAL MOBILITY OF BAFF-R WITHIN THE PLASMA
MEMBRANE 31
2.4 BAFF-R P21R PREDISPOSES FOR CVID BUT IS LESS FREQUENT IN CLL
PATIENTS 31
2.5 P21R REDUCES
NF-KB
ACTIVATION,
B
CELL SURVIVAL AND IGM SECRETION 34
2.6 BAFF-R H159Y MUTATION COMPENSATES P21R 38
2.7 P21R IMPAIRS TL IMMUNE RESPONSES TO PNEUMOCOCCAL POLYSACCHARIDES 39
3 DISCUSSION 42
3.1 PRE-LIGAND ASSEMBLY OF BAFF-R IS A PRE-REQUISITE FOR BAFF BINDING 42
3.2 THE H159Y MUTATION IS LINKED TO P21R BAFF-R 48
3.3 THE INFLUENCE OF THE P21R MUTATION ON MZ B CELL RESPONSES 50
3.4 P21R - A MODIFIER OF DISEASE DEVELOPMENT 52
4 MATERIALS AND METHODS
57
4.1 MOLECULAR BIOLOGICAL METHODS 57
4.1.1 AGAROSE GEL ELECTROPHORESIS 57
4.1.2 PLASMID DNA PREPARATION 57
4.1.3 DETERMINATION OF DNA CONCENTRATION 58
4.1.4 DNA CLEAVAGE BY RESTRICTION ENDONUCLEASES 58
4.1.5 LIGATION OF DNA 58
4.1.6 KLENOW FILL IN REACTION 58
4.1.7 PRODUCTION OF CHEMICAL COMPETENT E. COLI 59
4.1.8 BACTERIAL TRANSFORMATION 59
4.1.9 SEQUENCING 60
4.1.10 PLASMIDS 60
HTTP://D-NB.INFO/1037692721
4.1.11 ISOLATION OF GENOMIC DNA 61
4.1.12 RESTRICTION FRAGMENT LENGTH POLYMORPHISM (RFLP) ANALYSIS 61
4.1.13 P21R-H159Y LINKAGE ANALYSIS 63
4.2 METHODS FOR CELL CULTURE 63
4.2.1 FREEZING AND THAWING OF CELLS 63
4.2.2 CELL CULTIVATION 64
4.2.3 DETERMINATION OF CELL NUMBERS 64
4.2.4 CELL TRANSFECTION 64
4.2.5 GENERATION OF BAFF-R EXPRESSING CELL LINES 64
4.2.6
NF-KB2
PROCESSING
IN
BAFF-R
EXPRESSING CELL LINES 65
4.2.7 PATIENTS AND HEALTHY DONORS 65
4.2.8 PURIFICATION OF HUMAN B CELLS AND PLASMA 65
4.2.9 GENERATION OF EBV LINES 66
4.2.10 IN VITRO B CELL ACTIVATION 66
4.2.11 ISOLATION OF MURINE B CELLS 66
4.2.12 MURINE B CELL IN VITRO TRANSDUCTION AND ACTIVATION 66
4.3 EXPERIMENTAL ANIMALS 67
4.4 BIOCHEMICAL METHODS 67
4.4.1 BAFF BINDING ASSAYS 67
4.4.2 KD, BMAX AND SCATCHARD ANALYSIS 67
4.4.3 PURIFICATION OF RECOMBINANT BAFF, CD40L UND IL21 68
4.4.4 PREPARATION OF CELL LYSATES FOR SDS-POLYACRYLAMIDE GEL
ELECTROPHORESIS 68
4.4.5 SDS-PAGE AND WESTERN BLOT ANALYSIS 69
4.4.6 PREPARATION OF CELL LYSATES FOR TWO DIMENSIONAL GEL
ELECTROPHORESIS 71
4.4.7 SEPARATION BY BN GEL ELECTROPHORESIS 71
4.4.8 DENATURATING SECOND DIMENSION 72
4.4.9 ANALYSIS OF RECEPTOR-LIGAND COMPLEXES 72
4.4.10 ENZYME LINKED IMMUNO SORBENT ASSAY (ELISA) 72
4.4.11 CALCULATION OF ANTIBODY TITERS 73
4.5 FLOW CYTOMETRY ANALYSIS 73
4.5.1 DETERMINATION OF CELL NUMBER BY FLOW CYTOMETRY AND TIMED
ACQUISITION 75
4.6 MICROSCOPY OF FLUORESCENT BAFF-R FUSION PROTEINS 75
4.7 FRET ANALYSIS 75
4.8 FLUORESCENCE RECOVERY AFTER PHOTOBLEACHING (FRAP) 76
4.9 STATISTICS 76
4.10 CHEMICALS 76
5 ABBREVIATIONS 80
6 LITERATURE 84
7 APPENDIX
97
DANKSAGUNG
|
| any_adam_object | 1 |
| author | Pieper, Kathrin |
| author_GND | (DE-588)1037692454 |
| author_facet | Pieper, Kathrin |
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| author_sort | Pieper, Kathrin |
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| dewey-hundreds | 600 - Technology (Applied sciences) 500 - Natural sciences and mathematics |
| dewey-ones | 610 - Medicine and health 570 - Biology |
| dewey-raw | 610 570 |
| dewey-search | 610 570 |
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| dewey-tens | 610 - Medicine and health 570 - Biology |
| discipline | Biologie Medizin |
| format | Thesis Book |
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| spelling | Pieper, Kathrin Verfasser (DE-588)1037692454 aut A common SNP in BAFF-R impairs receptor multimerization, predisposes to immunodeficiency but reduces the risk to develop chronic lymphocytic leukemia vorgelegt von Kathrin Pieper 2013 97, 13 Bl. Ill., graph. Darst. txt rdacontent n rdamedia nc rdacarrier Enth. 1 Zeitschriftenartikel aus J Allergy Clin immunol 2013 Freiburg (Breisgau), Univ., Diss., 2013 (DE-588)4113937-9 Hochschulschrift gnd-content DNB Datenaustausch application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=026227624&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis |
| spellingShingle | Pieper, Kathrin A common SNP in BAFF-R impairs receptor multimerization, predisposes to immunodeficiency but reduces the risk to develop chronic lymphocytic leukemia |
| subject_GND | (DE-588)4113937-9 |
| title | A common SNP in BAFF-R impairs receptor multimerization, predisposes to immunodeficiency but reduces the risk to develop chronic lymphocytic leukemia |
| title_auth | A common SNP in BAFF-R impairs receptor multimerization, predisposes to immunodeficiency but reduces the risk to develop chronic lymphocytic leukemia |
| title_exact_search | A common SNP in BAFF-R impairs receptor multimerization, predisposes to immunodeficiency but reduces the risk to develop chronic lymphocytic leukemia |
| title_full | A common SNP in BAFF-R impairs receptor multimerization, predisposes to immunodeficiency but reduces the risk to develop chronic lymphocytic leukemia vorgelegt von Kathrin Pieper |
| title_fullStr | A common SNP in BAFF-R impairs receptor multimerization, predisposes to immunodeficiency but reduces the risk to develop chronic lymphocytic leukemia vorgelegt von Kathrin Pieper |
| title_full_unstemmed | A common SNP in BAFF-R impairs receptor multimerization, predisposes to immunodeficiency but reduces the risk to develop chronic lymphocytic leukemia vorgelegt von Kathrin Pieper |
| title_short | A common SNP in BAFF-R impairs receptor multimerization, predisposes to immunodeficiency but reduces the risk to develop chronic lymphocytic leukemia |
| title_sort | a common snp in baff r impairs receptor multimerization predisposes to immunodeficiency but reduces the risk to develop chronic lymphocytic leukemia |
| topic_facet | Hochschulschrift |
| url | http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=026227624&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |
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