chapter 6 Flashcards
B cells use groups of PARTS of genes to create
different possible antibodies using _____________________
recombination
What are the different gene segments that undergo recombination?
variable (v)
diversity (d)
joining (j)
constant (c)
Which segments are used in antibody heavy chains only?
D segments
What gene segments are included on Kappa light-chain?
V, J, and C
How many Vk gene families and Jk segments do mice have?
18 and 4
Lambda light-chain genes pair each ________segment with a
particular ________ segment
J
C
Only 5% of mouse Igs have lambda light chains due to ________________
a loss of most of the Vλ segments
In humans, what percent of light chains are lambda type?
40%
What segments are included on the heavy chain?
V, D, J, and C
-flank each antibody gene segment
-has a conserved nonamer and heptamer sequence
recombination signal sequences (RSS)
In between the nonamer/heptamer lies either a _____________ sequence
12 or a 23 bp spacer
what is the “12/23 rule?”
the spacing and arrangement dictates that a 12 bp RSS must pair with a 23 bp RSS for recombination to occur.
In between the nonamer/heptamer sequence lies ____________________________
either a 12 or a 23 bp spacer sequence
What enzyme joins the gene segments?
RAG1/2 recombinase
What does RAG stand for?
recombination activating gene
Which RAG is more important?
RAG1; it forms a complex with RSSs stabilized by
binding RAG2
V(D)J recombination results in a functional Ig ________________
variable region gene
How can V(D)J recombination occur between segments
transcribed in either the same or opposite directions?
So long as the correct RSSs are lined up, orientation of the actual gene segment is irrelevant
What are the 5 mechanisms that generate antibody diversity in naive B cells?
- multiple gene segments
- P nucleotide addition
- exonuclease trimming
- non-templated N nucleotide addition
- combinatorial diversity
multiple gene segments determines what?
which gene segments are put together
templated nucleotide addition between joints, resulting from asymmetrical cleaving of hairpin structures
P nucleotide addition
sometimes occurs at junctions, losing nucleotides and changing reading frames
exonuclease trimming
mediated by TdT activity, adding in random nucleotides between joints
Non-templated N nucleotide addition
combinatorial diversity determines what?
which heavy chains pair with which light chains
ensures that each B cell synthesizes only one heavy and one light chain
allelic exclusion
Describe the ordered heavy/light chain recombination process:
-heavy chains and recombined and expressed first
-expression of a functional heavy chain shuts down recombination machinery temporarily
-the heavy chain is paired with a surrogate light chain to form a pre-BCR
-if that works, then the machinery is started back up and light chain takes place
Nonreproductive arrangements can lead to what during development?
apoptosis
receptor editing of potentially ______________receptors occurs in light chains.
autoreactive
which two antibodies are expressed by mature B cells?
IgM and IgD
how is mRNA splicing involved in expression of IgM and IgD antibodies?
it removes the intervening spacer between VDJ and C, leaving VDJC mRNA ready to be translated
Primary transcripts for IgM heavy chains may result from _______________ transcribing through both the IgM and IgD constant regions
RNA polymerase
The _________________ are similar in structure to the antibody light chain
α and γ chain
The _______________ are similar in structure to the antibody heavy chain
β and δ chain
