MBIO - Lecture 10

• A: starts in the germ line
• B: B cell DNA transcribed into Transcribed RNA then RNA splicing splices into Spliced mRNA which is then translated into a light chain protein
• C: heavy chain protein

• 2 types of signal secuences
• one has a 12bp spacer (surrounded by a 7mer and a 9mer)
• second has a 23bp spacer (surrounded by a 7mer and a 9mer)
• A: recombination signal sequences
• B: single strand cleavage
• C: herapin formation
• D: herapin opening fusion conde of segments-->further recombination
• D2: single joint formation-->DNA non homologous end joining proteins--> discarded

rag1 and rag 2 bind to the signal sequences to for a hair pin loop

• extrinsic damage: ultraviolet radiation, drugs, (ROS), (IR)
• intrinsic damage: VDJ recombination, Class switching recombination (CSR), Somatic hyper mutation (SHM)
• Other damage: telomere shortening, aging
• Sensing: variety of sensing proteins
• Signal transduction:
• Outcome: Senesence(P53), Apoptosis(P53), transcriptional response, cell cycle arrest, DNA repair

• Bone Marrow:
• Blymphocyte development: VDJ recombination, proliferation, ROS, telomere shortening
• Hemapoptoetic stem cells: selfrenewal, proliferation, ROS, telomere shortening
• Thymus:
• T lymphocyte developement: VDJ recombination proliferation, ROS, telomere shortening
• Secondary Lymphoid Organs:
• B lymphocytes:CSR, SHM, Clonal expansion, ROS, Telomere shortening
• T lymphocytes: endegenous proliferation and clonal expansion, ROS, telomere shortening

• hypomorphic: loss of most function but retains some residual function (like a null allele)
• types of mutations:
• Artemis
• DNA-Lig 4
• Cemunnos

• Deamination: activation induced deamination, switches thymine to uracil
• damaging the dna can also lead to improperly placed bps which contribute to dna diversity

in the CSR pathway: activation induced deaminase

Generatng mutatons to enhance diversity in the immune system

translesion proteins and enzymes have less accuracy in putting bps thus contributing to dna diversity