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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
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Which stages of B cell development are antigen indep?
Lymphoid stem cell--->Mature B cell
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Which stages of B cell development are antigen dep?
Activated B cell--->Plasma cell
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When is IgM first expressed?
in pre-B cell stage, only mu H chain is expressed
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What happens at the immature B cell stage?
- 1. L chains are made and interact with H chains
- 2. tolerance induction
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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
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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)
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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)
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How many gene segments do H chains have?
4: V, D, J, C
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How many gene segments do L chains have?
3: V, J, C
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What is the order of gene rearrangement for the H chain?
- 1. D to J
- 2. V to DJ
- 3. VDJC
*H chain expressed before L chain (pre-B)
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What is the order of gene rearrangement for the L chain?
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RSS
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
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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
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Junctional diversity
P and N nuc additions results in imprecise joining of ends and presence of variation (see notes for mech)
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What is a pot conseq of junctional diversity?
reading frame shift: leads to a non func antibody prot; called non-productive rearrangements
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What is the role of RAG?
cleaves chains to result in hairpins at the end of each DNA strand at coding ends
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What is the role of Artemis-DNA-Pk?
opens hairpins in junctional diversity, making a palindromic seq
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What is the role of TdT?
N nuc additions to palindromic ends created by artemis-DNA-Pk
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Allelic exclusion
expression of a gene from only one of two chromosomes encoding that gene; occurs for H and L chains
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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.
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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
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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)
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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
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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
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What are the components of TCR?
- acidic a chain dimer
- basic B chain dimer
- glycoproteins
- TM region
- cytoplasmic tail
- V and C regions w/in each a and B chain
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What is the less common form of TCR?
gamma/delta TCR; not MHC restricted; can recog antigens w/ non-classical MHC molecules
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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
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B chain gene organization
V, D, J, C region domains (analogous to H chain of Ig)
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a chain gene organization
V, J, C region domains (analogous to L chain of Ig)
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