MS1/Mod 1: immunology; B cell development and differentiation
What are the stages of B cell development?
Lymphoid stem--->pro-B--->pre-B--->immature B cell--->mature B cell--->activated B cell--->memory B cell--->plasma cell
Which stages of B cell development are antigen indep?
Lymphoid stem cell--->Mature B cell
Which stages of B cell development are antigen dep?
Activated B cell--->Plasma cell
When is IgM first expressed?
in pre-B cell stage, only mu H chain is expressed
What happens at the immature B cell stage?
1. L chains are made and interact with H chains
2. tolerance induction
How does a B cell transition to mature B cell stage?
the B cell is able to express IgM AND IgD on its surface; monospecific
How does a B cell become an activated B cell?
by specific antigen; can now proliferate and secrete IgM; class switching can now happen (un altre' classe possono mostrare adesso)
Why do plasma cells typically have lots of rER?
bc always secreting antibodies at high rates (presence of polyribosomes and vesicles and active golgi as well)
How many gene segments do H chains have?
4: V, D, J, C
How many gene segments do L chains have?
3: V, J, C
What is the order of gene rearrangement for the H chain?
1. D to J
2. V to DJ
*H chain expressed before L chain (pre-B)
What is the order of gene rearrangement for the L chain?
1. V to J
recombination signal seq: highly conserved 7bp and 9bp seq that are directly adj to each Ig gene segment (V, D, J)
recog by RAG prot
What is the rule for recombination?
the seq btw the RSSs flanking the VDJ regions must be of diff lengths; only 12/23 pairings
spacer seq are NOT conserved whereas RSSs are conserved
P and N nuc additions results in imprecise joining of ends and presence of variation (see notes for mech)
What is a pot conseq of junctional diversity?
reading frame shift: leads to a non func antibody prot; called non-productive rearrangements
What is the role of RAG?
cleaves chains to result in hairpins at the end of each DNA strand at coding ends
What is the role of Artemis-DNA-Pk?
opens hairpins in junctional diversity, making a palindromic seq
What is the role of TdT?
N nuc additions to palindromic ends created by artemis-DNA-Pk
expression of a gene from only one of two chromosomes encoding that gene; occurs for H and L chains
Why are most B cells lost during H chain synth?
H chain is first one to be rearranged (V-DJ only bc D-J does not participate in rearrangement); if first strand not successful, then attempts at second strand; if second strand not successful then cell dies.
Why are B cells more likely to have K-L chains than L-L chains?
K-L chains rearrange before L-L chains are given a chance to rearrange; L-L chains only given a chance if K-L chains fail to rearrange at both strands
How is membrane bound Ig diff from secreted Ig?
-contains phobic TM tail and cytoplasmic tail at carboxyl end
-each receptor assoc w/ two Ig-a an Ig-B heterodimers (have TM and cytoplasmic tails for signaling into B cell)
What is the sig of alt RNA processing in Ig formation?
genes for TM and cytoplasmic tails are on genes for both secreted and membrane form of Ig; diff is which cleavage and polyadenylation sites are recog
How are IgM and IgD genes regulated?
mu and delta genes are both on B cell genome; diff is during processing of pre-mRNA
IgD present on mature B cells (low amts on immature) in higher amts than IgD on mature cells
What are the components of TCR?
acidic a chain dimer
basic B chain dimer
V and C regions w/in each a and B chain
What is the less common form of TCR?
gamma/delta TCR; not MHC restricted; can recog antigens w/ non-classical MHC molecules
What mem prot assoc w/ TCR?
TM extracellular gamma, delta, epsilon (x2): CD3 complex (ALWAYS PRESENT..needed to transmit signal to inside of cell)
TM intracellular zeta chain dimer
B chain gene organization
V, D, J, C region domains (analogous to H chain of Ig)
a chain gene organization
V, J, C region domains (analogous to L chain of Ig)