Transcript Rearrangement

Rearrangement
The normal process by which
antibodies and T cell
receptors are made
So What Is a Rearrangement?

Rearrangement is a term used to describe a
recombination of DNA within a single
chromosome.
Rearrangement
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Remember that every immunoglobulin
molecule and every TCR contains both a
variable region and a constant region and
that the variable region is the part of the
molecule that interacts with the antigen.
TCR = T cell receptor
Immunoglobulin = Antibody = B cell receptor (BCR)
What is meant by the term
rearrangement in relation to DNA?
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Antigen independent maturation of B and T
cells to immunocompetent B and T cells that
express receptors for antigen recognition
involves a rearrangement of the cell’s
germline DNA.
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Germline DNA = DNA that is an exact sequence
replicate of the genome present at fertilization of
egg by sperm. It has not been rearranged.
Most cells in the body maintain copies of
germline DNA.
Rearrangement continued
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The genes that code for the different chains
of the B and T cell receptors include a large
number of exons.
The exons that code for the variable regions
of the immunoglobulin molecules and TCRs
are called the variable (V) segments,
diversity (D) segments, and junctional (J)
segments, and those that code for the
constant regions are called the C segments.
Shematic of
germline genes
for TCR alpha
and beta and
immunoglobulin
heavy and kappa
light chains
Note how large a
number “n” is!
Rearrangement continued
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For the immunoglobulin heavy chain, there
are 100-200 different V regions, 30 different
D regions, 6 different J regions, and 9
different C regions.
For the TCR beta chain, there are 75-100
different V regions, 2 different D regions, 13
different J regions, and 2 different C regions.
Note: these numbers are more current than
those on the preceding schematic.
Change V1 to
Vn in the right
hand column.
Rearrangement continued
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The first step in the rearrangement process
involves the the apposition of one D
segment of the gene with one J segment by
deletion of all intervening sequences, both
coding and non-coding (a DJ
rearrangement).
In a similar process a V segment becomes
apposed to the DJ rearrangement to form a
VDJ rearrangement.
Rearrangement continued
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After rearrangement of the DNA,
transcription occurs.
Subsequent splicing of the primary transcript
with deletion of noncoding sequences
results in apposition of VDJ to C coding
regions to form a mature VDJC mRNA
which can be translated into an
immunoglobulin heavy chain or TCR.
Gene Rearrangements
to make an antibody
Remember: this rearrangement is happening in the gene –
not during RNA processing.
Can you list multiple inaccuracies in this animation?
Rearrangement continued
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Once the productive rearrangement occurs
on one chromosome, an active protein chain
is synthesized and it provides a trigger to
prevent rearrangement of the other allele
(allelic exclusion).
Thus each B or T cell expresses only one
immunoglobulin or TCR, respectively.
Rearrangement continued
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This complex process of
rearrangement allows for tremendous
diversity of both the cell-mediated and
humoral arms of the immune system,
and the ability to respond to a wide
array of antigens.
Review: How do translocation and
rearrangement differ?
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Translocation is the recombination of
DNA between two different
chromosomes. Rearrangement is the
recombination of DNA within a single
chromosome (and within a single
gene).
Translocations are abnormal.
Rearrangements of genes for
immunoglobulins and TCRs are
normal.