Lymphocyte Dev. & Ag Receptor Gene Rearrange Test II Flashcards
Maturation of B and T cells occurs in Generative Lymph organs what are the events?
Commitment of progenitor cells to B or T lineage.
Proliferation of progenitors and immature lymphocytes.
Sequential and ordered Rearrangement of Ag receptor genes and expression of BCR or TCR proteins.
Selection events, delete self reactive cells
Differentiation of B and T cells into functionally and phenotypically distinct cells.
What can Pro-B cells differentiate into?
FO B cells
MZ B cells
B1 cells
What can Pro-T cells differentiate into?
aB T cells
yDelta T cells
NK cells
In the Thymus and Bone marrow stromal cells produce ____ which drives proliferation of T cell progenitors and stimulates B cell development.
IL-7
Development of NK cells occurs in the thymus and depends on what cytokine?
IL-15
In the early commitment to B cells lineage what is the first thing that occurs?
The Ig heavy chain locus opens up and is available to proteins tha mediate Ig gene rearrangement and expression.
What TF commit developing lymphocytes to the T cell lineage?
Notch-1 and GATA-3
What TF induce edxpression of genes needed for B cell development?
E2A and Pax-5`
Describe Allelic Exclusion.
L and H chains of Ig are codominantly inherited and only one of the light and heavy chain alleles can be expressed in a single B cell. Rearrangement of maternal and paternal alleles starts simultaneously but expression depends on which set finishes first and that one will be expressed.
What determines variable regions of chains in B and T cell receptors?
Rearrangement of DNA. This includes deletions of DNA/RNA nucleotides and reannealing of the segments, through Rag1 and Rag2 recombination enzymes.
What re the three mechanisms of Receptor diversity?
Somatic Recombination
mRNA splicing
Junctional diversity
Explain how Rag1 and Rag2 work.
Rag 1 and Rag 2 initiate V(D)J recomb by indroducing double stranded breaks in DNA. Rag mediated breaks are resolved by NHEJ.
What does recombination of B cells start with?
Heavy chain in B cells (Beta chain in T cells). If the recombination is functional the rearrangement of light chain K or L occurs in B cells. (alpha chain in T cells)
How is BCR diversity achieved?
First D and J are randomly chosed and DNA between is deleted.
Second, a V segment is chosen and DNA between V and DJ is deleted.
Third, C is chosen and DNA between VDJ and C is deleted.
Chances of producing a fxnl rearrangenment is 10% there will be a test for productive rearrangement and once thats confirmed competition between maternal and paternal H chains is over recombination is stopped.
What does TdT do?
Adds or removes nucleotides to exposed ends of V D or J genes before they are reunited. It further increases the diversity of TCR and BCR’s
Junctional Diversity results from the loss and addition of what?
Loss of nucleotides through exonucleases and addition of N and P nucleotides
During lymphocyte development cells go through multiple checkpoints for selection what are they?
- after produciton of first polypeptide chain of 2chain
Ag receptor is complete. - Follows production of second polypeptide chain the Ag receptor is completed
Checkpoints ensure that only lymphocytes that are successful in Ag receptor rearrangement can mature
Pre-BCR’s contain what chain?
IgM heavy chain
Pre-TCR’s contain what chain?
TCR B chain
What is the first Ag receptor gene to be completely rearranged in B cells?
Ig heavy chain. Once this is successfully rearranged they express IgM heavy chain and assemble pre-BCR
If cells make out of frame rearrangements what happens?
They dont receive survival signals and undergo apoptosis
If B cells have high affinity for self Ags after first rearrangement what happens?
They undergo the second attempt in gene rearrangement called receptor editing. If editing fails the second time then the B cells die.
What kind of B cells do B cells that develop from the fetal liver differentiate into?
B-1 Lineage
B lymphocytes that arise from bone marrow precursors after birth give rise to what lineage?
B-2 lineage
Why is there no junctionanl diversity in B 1 cells?
TdT is not expressed in the fetal liver and TdT results in junctional diversity
Where are a large number of B1 cells found?
In the peritoneum and mucosal sites, they are a self renewing population
What type of Abs are present without overt immunization?
“Natural Antibodies”. B1 cells spontaneously secrete IgM that interacts with polysaccharides and lipids and oxidizes them. B1 contribute to most of serum IgM at initial infection
What do immature B2 cells differentiate into?
MZ B cells: abundant in spleen can be found in LN too
FO b-2 cells: recirculating lymphocytes
What do MZ B cells do?
localize to spleenic marginal zone and respond to blood borne Ags
What type of B cell develops into long lived plasma cells or memory B cells?
Only mature FO B-2 cells after T cell dependent activation
What B cells are independent of T cell help?
MZ B cells
MZ B cells respond to what type of infection, and differentiate into what?
Blood borne microbes and they differentiate into short lived IgM secreting plasma cells
About 90% of developing T cells become what type?
aB T cells.
Why is there limited diversity of yDelta T cells?
Only a few of the available VdJ segments are used in mature gamma delta T cells
