Lecture 6 Flashcards
What is major rule of antibody synthesis?
- Single B cell only makes one type of antibody
- Occurs by allelic exclusion
- Same is true for plasma cell
- Only one type of H chain and one type of L chain
What has occured in ProB cell?
- Heavy DJ rearrangement
- No light chain rearrangement
When does DJ rearrangement occur?
ProB stage
What do mature B cells have on surface
IgM & IgD with same variable region
What mediates VDJ rearrangement?
RSS
What do RAG1/2 do?
Enzymes that recognize and align RSS and cleave sequence between
Are all RAG rearrangements functional?
No
How do IgM and IgD end up on same cell?
Alternative splicing of nuclear RNA
What is junctional diversity?
- N region addition
- Nucleotides (B sequences) not present in germ line that are added to junctions of rearranged VDJ during rearrangement
- Adds to diverstiy
What facilitates junctional diversity?
TdT
3 contributions to Ig Diversity?
- VDJ rearrangement
- Junctional diversity
- Combination of H & L chain
What happens to non functional VDJ rearrangements?
They are deleted
What happens to self reactive B cells?
- Become anergic
- Deletion
- Rescued by receptor editing
What happens to self reactive B cells?
- Become anergic
- Deletion
- Rescued by receptor editing
Where does isotype switching occur?
In periphery, not in marrow
What causes isotype switching?
B cell interaction with antigen
What can isotype switch result in?
IgG
IgE
IgA
What is necessary for isotype switch?
- AID - Enzyme that will cleave loop
- Cleaved region is ligated associating VDJ region with new gene
- Cleaved region is deleted from genome
Can B cell undergo multiple isotype switches?
Yes
Where does generation of antibody diversity occur?
Generation of antibody diversity occurs in bone marrow in antigen independent manner