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36 Cards in this Set
- Front
- Back
In which phase of B-cell development do B-cells acquire functional antigen receptors thru immunoglobulin gene rearrangements? Where does this occur?
(pg 159) |
Phase 1 in the bone marrow
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During which phase of B-cell development do the B-cells leave the bone marrow?
(pg 159) |
Phase 2- negative selection begins in the bone marrow and continues as B-cells leave the bone marrow and travel to secondary lymphoid tissues
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In which phase of B-cell development does negative selection occur?
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second phase (begins in bone marrow)
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In which phase of B-cell development does positive selection occur? What does + selection refer to?
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Phase 3- occurs in secondary lymph tissue
+ selection= process in which B-cells compete for limited # of sites in follicles of secondary lymphoid tissues |
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What are anti-CD34 monoclonal antibodies used for
(pg 160) |
to separate hematopoietic stem cells from other bone marrow cells for use in therapeutic transplantation
CD34 is present on ALL human hematopoietic stem cell |
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What are the earliest identifiable cells of the B-cell lineage?
(pg 160) |
pro-B cell
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What is the main event in the pro-B-cell stage?
(pg 160) |
rearrangement of the heavy-chain genes
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Which comes first; rearrangement of heavy-chain genes or light-chain genes?
(pg 160) |
heavy-chain genes ALWAYS comes first
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In which stage of B-cell development in the bone marrow does D-J gene rearrangements occur?
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early pro-B-cell stage
"get a DJ (early pro-B-cell) then V-DJ (late pro-B-cell)" |
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In which stage of B-cell development in the bone marrow does V- DJ gene rearrangements occur?
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LATE pro-B-cell stage
"get a DJ (early pro-B-cell) then V-DJ (late pro-B-cell)" |
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When is a cell considered a PRE-B-cell?
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once a B cell expresses a u chain
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In which cells do rearrangement of light chain genes occur?
(pg 161) |
small pre-B-cell
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What's the roles of stromal cells in the bone marrow in B cell development? (2)
(pg 161) |
1. cell-cell contact
2. growth factors |
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During B stem cell stage, what adhesive molecule on the stromal cell hold on to the stem cell?
(fig 6.5) |
VCAM-1: bind to VLA-4 on the stem cell
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During early pro-B cell stage, what adhesive molecule on the stromal cell hold on to the early pro-B cell?
(fig 6.5) |
SCF: bind to Kit on the early pro-B cell
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What important growth factor does stromal cell secrete for B cell development?
What developmental stage does B cell receive this growth factor? (fig 6.5) |
IL-7
Late pro-B cell: IL-7 receptor expressed |
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What are non-productive rearrangements?
productive rearrangements? (pg 162) |
gene rearrangements that do not translate into a useful protein
rearrangements that preserve a correct reading frame & give rise to a complete & functional Ab chain |
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For an early pro-B cell to rearrange the immunoglobulin heavy chain genes it must express what genes?
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RAG-1 & RAG-2, termed "recombination-activating" genes
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What 2 criterion must pro-B cells demonstrate to survive?
(pg 163) |
1) make a u heavy chain
2) u chain must demonstrate the ability to combine with immunoglobulin light chain |
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What is the surrogate light chain composed of?
(pg 163) |
VpreB and λ5
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Do VpreB and λ5 genes rearrange?
(pg 164) |
No
also note they are separated from the immunoglobulin loci |
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What transcription factors control transcription of VpreB and λ5 genes?
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E2A & EBF
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What is allelic exclusion?
(pg 164) |
phenonmenon in which a cell expresses only one of its copies of a gene (ie in B-cell development, the second immunoglobulin heavy-chain is not expressed if the first one is expressed correctly)
fig 6.8 |
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Why is rearrangement of the light chains by pre-B cells relatively more efficient than rearrangement of heavy chains by early pro-Bcells? What is the consequence of increasing efficiency?
(pg 165) |
only a single event joining V & J is needed to rearrange a light-chain gene
(2 recombination events are needed to bring together V, D & J regions of heavy-chain) this increases efficiency but reduces diversity |
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Are there functional differences between k and λ light-chain isotypes?
(pg 165) |
Nope
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Why 2/3 κ chain and 1/3 λ chain?
(pg 164) |
Because κ gene is rearranged first before the λ gene
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What are the two check points in B cell maturation?
(pg 167) |
1. surface expression of H chain with surrogate L chain and Igα:β ensures functional H chain production.
2. surface expression of BCR and Igα:β turns of further L chain rearrangement and ensures functional L chain production. |
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Why are RAG1 and RAG-2 genes turned off in B-cell development? In which stage are they turned off?
(pg 168) |
proliferation, no recombination.
large pre-B cell |
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When is Igα:β heterodimer genes turned off?
(pg 168) |
When B cell differentiates into plasma cells when they do not make surface Igs.
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What is the function of Btk?
(pg 170) |
Bruton's tyrosine kinase: signal transduction molecule needed for development of pre-B cell to immature B cell.
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What is X-linked agammaglobulinemia caused by?
(pg 170) |
lack of Btk.
no antibodies. recurrent infection with common extracellular bacteria |
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What are proto-oncogenes?
(pg 171) |
genes that cause cancer when their function and expression is preturbed.
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What is an oncogene?
(pg 171) |
viral genes that transform normal cells to tumor cells directly.
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What's the cause of Burkitt's lymphoma?
(pg 171) |
MYC gene on chromosome 8 transloated with Ig gene on chromosome 14(H chain) or 22(λ L chain), or 2(κ L chain).
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B cell tumor is often caused by the translocation between an Ig gene and a _____.
(pg 171) |
proto-oncogene.
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Which of the following are proto-oncogenes:
A. MYC B. BCL2 C. Both D. Neither |
C.
MYC: regulate cell cycle BCL2: prevent premature apoptosis |