Antigen Receptor B-Cell Development Lecture 5 Flashcards
Early Pro-B cell
Heavy chain DJ rearrangment
Late Pro-B
Heavy chain V-DJ rearrangement
Large Pre-B
mu chain transiently at surface as part of pre-B-cell receptor. mainly intracellular
-mu heavy chain that is made binds a surrogate light chain and takes it to the surface
small pre-B cell
V-J rearranging
-intracellular mu chain
immature B-cell
IgM expressed on cell surface
Mature B cell
IgD and IgM made from alternatively spliced Heavy chain transcripts
What does RAG recognize and what does it do?
RAG recognizes RSS and cleaves the DNA between RSS and J or RSS and V, come together and get ligated
What is a brec
B cell Recombination excision circle
How do you get secreted IgM and membrane IgM with the same VDJ region? And IgM and IgD with the same VDJ region?
Alternative RNA splicing
Does class switch happen in the bone marrow?
NO
-in the periphery, using aid mediated cleavage
How do we get such a large repertoire of Ig?
3 reasons
- combinatorial V(D)J gene joining
- N nucleotide addition by TdT
- Combinatorial association of H and L chains
What does TdT do?
randomly puts on nucleotides to either side
can be anywhere from 1 to 30
changes antibody site-doesn’t require any additional DNA
What are three ways these VDJ gene rearrangements may react with self, what happens to them?
- multivalent self molecule
- soluble self molecule
- no self reaction
What are three ways these VDJ gene rearrangements may react with self, what happens to them?
- multivalent self molecule
- clonal deletion-apoptosis or receptor editing - soluble self molecule
- migrates to periphery-low mu expression-anergic bcell - no self reaction
- migrates to periphery-mature b cell
How is a multivalent self molecule given a second chance? (self-reactive b-cell)
receptor editing
- up regulate RAG-can rearrange again
- this can only happen in the light chain because in the heavy chain all the other d’s are deleted