Lec 16: B cell DADM Flashcards
VDJ recombhination
process by which T cells and B cells randomly assemble different gene segements
variable V, diversity D, and joining J regions
generates unqiue receptors (known as antigen receptors) that can collectively recognize many different types of molecuels
requries the activity of RAG1/2 compelx
consider VDJ recombination of light and heavy chains
bruh idk
multiple gene segements
VDJ segment recombination provides extensive combinatoral diveristy
P nucleotide addition
adds a short palindromic sequence at the join
allows for the coding of more peptides
Exonuclease trimming
loss of nucleotides at the joints
loss of aa = end up with a different sequence
non-tempalte N nucleotide additon
facilitated by TdT enzyme, up to 20 extra nuclotides can be added at the joints of heavby chain genes
combinatoral diversity
same heavy chain can combine with different light chains and vise versa
somatic hyper mutation
through the activity of an enzyme called activation induced (cytidine) deaminse (AID) and DNA repair process, the variable regions of IG-BcR locus ar emutated
lots leads to frameshift mutations, and thus the loss of a functional BcR
However can lead to new affinity/ a higher affinity for something you otherwise couldn’t code for
Class-switch recombination
CSR
process by which immunoglobulin heaavy chain locus contant region is changed, but the variable region remains the same (this is also called isotype swithing)
- > does not alter antigen specificity
- > central to the maturation of the antibody resposne
- > crucially requires cyidine deaminase AID
- > is an irreverible process
B cell development and clonal selection
clonal selection hypthesis:
each B cell bears a singal type fo BcR
*Upon stimulation, each cell will create a clone of cells bearing the same Ag receptor as the original
activated B cells can become antibody secreting plasma cells or memoty B cells
memory cells retain thier BcR, howver plasma lose them and secrete them instead
B cell antigen recognition
bcr clustering induces internalization and antigen presentation by b cell
Inital interactions induce a clustering of bcr and ther cognate antigens
- > antigen binding induces conformational change in cu4domain -> oligomerization of antigen-bound igM moleucles
- > antigen ahbound bcr moved into lipid rafts of the membrane -> allows for association of bcr signalling molecules -acitvation signal
bcell membrane rapidly spreads over the target membrane before contracting back
-> the entire process takes only minutes to comples
bcr causes smac formaiton
coordinated cell signalling and antigen extraction
b cells can capture membrane bound antigens from other APCs
T cell-depended B cell responses
classical Bcell activaion
B-cell bind antigen via bcr
within secondary lymphoid organs, inteaction with Th cells provides co-stimulation and cytokines for differentiation and memory cell production
T cell-depended B cell responses
B-cell bind antigen via bcr
antigen recognition by mature B cells provides a survival signal
if B cell doesn’t encounter its cogante Ag, it will die by apoptosis within moths after emerging from the bone marrow. ( tonic Bcr singlalling generaties a survival response)
inital activationa nd proliferation events
some antigen is internalised, processed and presented on MHCII
-> exogenous antigen (needs to be internalized and processes)***
T cell-depended B cell responses
within secondary lymphoid organs, inteaction with Th cells provides co-stimulation and cytokines for differentiation and memory cell production
B celles express CCR7 after antigen processing
B cells move into T cell rich zone until they encounter and interact with theri counterpart antigen-specific T cell
Bcells then down-regulate CCR7, leave Tcell areas and enter follicles
->innitial for mation of a GC
-> internalization and prossecing of antigen
=many different peptides
=many Th cells could activate the Bcells
=many novel peptides processed and presented on MHCII
-> many different T cells could recognize
BcR and TcR dont recognize the same thing
