generation of diversity in Igs 2
Terms
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- Ag exposure leads to what 2 general processes?
- Affinity maturation and Clonal selection
- what changes occur after Ag exposure in regards to Ig production?
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incr secreted: mbr-bound Ig ratio
somatic hypermutation
incr affinity of Ig for Ag
class switching - what is somatic hypermutation?
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SHM: point mutations
occurs in ALL CDR REGIONS (v. only CDR3 in recombination) - where does SHM take place?
- SHM occurs in 2ndary lymphoid follices; specifically GERMINAL CENTERS
- where is SHM occurring with the greatest freq?
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SHM occurs primarily near genes for the variable region
freq of SHM decreases as move away from V(D)J gene region - what are some consequences of SHM?
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can incr or decr biding affinity;
have no effect
increase diversity
generation of stop codons, missense
NO FRAMESHIFTS! - what is clonal selection?
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hypermutating B cells test new Igs on Ag-Ig complex on dendritic cells
incr affinity-> B cell received survival signal
decr affinity-> B cell dies - what happens with serial Ag exposure?
- cont Ag exposure results in an incr in the freq of mutations in CDR 1 and 2!!
- what is receptor revision?
- if, after SHM, B cell reacts with self, has the option to change V region before being killed
- what does isotype switching depend on?
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cytokines rel by T cells
microenvironment - what does isotype switching involve?
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translation of H chain C-region genes
"looping out" and loss of DNA
maintains specificity and affinity of V-region
incr fxnal diversity of Ig - what happens if an IgM-prod B cell does not receive signals from TH cells?
- B cell will cont to express and secrete only IgM
- what happens if B cell receives signals from TH cells?
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class-switching!
recombination of switch regions
looping out of intervening DNA
--> Ig with new heavy chain C-region - what are switch regions?
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areas of recombination between genes coding for diff Ig classes
NO switch region between IgM and IgD-->no IgD expression after Ag exposure - what occurs during post-transcriptional processing of primary mRNA for Ig?
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remove introns and J gene segments
RNA splicing of exons
leader seq dir mRNA to ER for assembly