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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
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
In which phase of B-cell development does negative selection occur?
second phase (begins in bone marrow)
In which phase of B-cell development does positive selection occur? What does + selection refer to?
Phase 3- occurs in secondary lymph tissue
+ selection= process in which B-cells compete for limited # of sites in follicles of secondary lymphoid tissues
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
What are the earliest identifiable cells of the B-cell lineage?
(pg 160)
pro-B cell
What is the main event in the pro-B-cell stage?
(pg 160)
rearrangement of the heavy-chain genes
Which comes first; rearrangement of heavy-chain genes or light-chain genes?
(pg 160)
heavy-chain genes ALWAYS comes first
In which stage of B-cell development in the bone marrow does D-J gene rearrangements occur?
early pro-B-cell stage

"get a DJ (early pro-B-cell) then V-DJ (late pro-B-cell)"
In which stage of B-cell development in the bone marrow does V- DJ gene rearrangements occur?
LATE pro-B-cell stage

"get a DJ (early pro-B-cell) then V-DJ (late pro-B-cell)"
When is a cell considered a PRE-B-cell?
once a B cell expresses a u chain
In which cells do rearrangement of light chain genes occur?
(pg 161)
small pre-B-cell
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
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
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
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
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
For an early pro-B cell to rearrange the immunoglobulin heavy chain genes it must express what genes?
RAG-1 & RAG-2, termed "recombination-activating" genes
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
What is the surrogate light chain composed of?
(pg 163)
VpreB and λ5
Do VpreB and λ5 genes rearrange?
(pg 164)
No
also note they are separated from the immunoglobulin loci
What transcription factors control transcription of VpreB and λ5 genes?
E2A & EBF
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
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
Are there functional differences between k and λ light-chain isotypes?
(pg 165)
Nope
Why 2/3 κ chain and 1/3 λ chain?
(pg 164)
Because κ gene is rearranged first before the λ gene
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.
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
When is Igα:β heterodimer genes turned off?
(pg 168)
When B cell differentiates into plasma cells when they do not make surface Igs.
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.
What is X-linked agammaglobulinemia caused by?
(pg 170)
lack of Btk.
no antibodies.
recurrent infection with common extracellular bacteria
What are proto-oncogenes?
(pg 171)
genes that cause cancer when their function and expression is preturbed.
What is an oncogene?
(pg 171)
viral genes that transform normal cells to tumor cells directly.
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).
B cell tumor is often caused by the translocation between an Ig gene and a _____.
(pg 171)
proto-oncogene.
Which of the following are proto-oncogenes:
A. MYC
B. BCL2
C. Both
D. Neither
C.
MYC: regulate cell cycle
BCL2: prevent premature apoptosis