Dev of B-Cells Flashcards
Regions in Light Chain
V-region
J-region
Constant region
Regions in Heavy Chain
V-region
D-region
J-region
Constant region
How do we get tens of millions of possible Ig seq’s from a few thousand genes?
By random recombination of light and heavy chains
How are V, D, and J brought together?
Unique Ens are induced in dev B-cells
–>RAG 1 and RAG 2
How do RAG 1 and RAG2 function?
Each Ig gene segment has signal sequences
–>Which determine which segments can be joined to each other
What are P nucleotides?
They are found in ALL joining junctions
What are N nucleotides?
They are added by TdT enzyme found only in the developing B-cells in the pro-B stage after birth
- ->Add random nucleotides to V-D and D-J joins
- ->Found ONLY in heavy chain
- ->adding nucleotides until some overlap
What do P and N nucleotides do?
Add randomness to splice site
What causes IgM switch to IgD
Selective splicing of primary RNA transcripts
-IgD formed by selective splicing of an RNA that is transcribed from both IgM and IgD constant regions
What else can slicing control?
Determines whether a cell synthesizes mem bound Ig or secreted Ig
–>AS B cell becomes more active and starts secreting Ig, more of the transcripts EXCLUDE transmembrane domains
Class switching?
Occurs (except in IgD) when a variable region (VDJ) is joined to a new constant region
Somatic Hypermutation?
Targets the rearranged gene segments encoding the variable region
- during class switching the variable undergoes high rate of mutation
- LIMITED to variable region (VDJ) of Ig
What occurs as a result of somatic hypermutation?
Those mutations that yield A.As that IMPROVE binding to Ag are SELECTED for!
What En is involved in both class switching and somatic hypermutation?
AID –> Activation-Induced cytidine Deaminase
T-cell Receptor
How it is generated is similar to the mechanism of generation of Ig
-EXCEPT somatic hypermutation