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B Lymphocyte Development
8.3 at 1pm by Dr. Sturtevant
62
Immunology
Professional
08/03/2011

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Cards

Term
Where does negative selection of B cells occur?
Definition
bone marrow
Term
Where does positive selection of B cells occur?
Definition
secondary lymphoid tissue
Term
Name the distinguishing CD marker of a pluripotent hematopoietic stem cell.
Definition
CD34
Term
Name the cells in the B cell lineage.
Definition
pluripotent hematopoietic stem cell-> common lymphoid progenitor-> B cell precursor -> pro-B cell -> pre B cells -> B cell
Term
What gene segments rearrange in early versus late pro-B cells?
Definition
early- DH + JH rearrange; late- DJH + Vh
Term
Do B cells rearrange their heavy or light chains first?
Definition
heavy is always first
Term
When does a pro b cell become a pre b cell?
Definition
when ยต chain expressed
Term
In what stage of B cell development are IgMs first assembled?
Definition
pre B cell
Term
Where in the body does B cell gene rearrangement occur?
Definition
bone marrow
Term
Which comes first, large or small pre B cells?
Definition
large then small
Term
In what B cell type does VL-JL rearranging take place?
Definition
small pre B cells
Term
Stroma
Definition
supportive cells and connective tissue in an organ
Term
How do stromal cells in the bone marrow contribute to B cell development?
Definition
they provide CAMS (cell adhesion molecules) and growth factors
Term
T/F IL-7 is required for stimulation and proliferation of young B cells.
Definition
true
Term
What's the chance that a VDJ rearrangment will be correct?
Definition
1/3
Term
DJ rearrangement occurs in which B cells?
Definition
early pro B cells
Term
VDJ rearrangement occurs in which type of B cell?
Definition
late pro B cell
Term
In which cell is VJ for the light chain rearranged?
Definition
Small pre B cell
Term
What is the Ig status of a large pre B cell?
Definition
u heavy chain is made
Term
What is the Ig status of a small pre B cell?
Definition
u chain is made in the endoplasmic reticulum
Term
What is the Ig status of an immature B cell
Definition
u heavy chain, lamdba or K light chain, IgM on surface
Term
How is it possible that so many VDJ arrangments are productive when they are so randomly spliced?
Definition
there are DNA modifying enzymes and transcription factors that fine tune B cell development. People with genetic defects in these manifest as immunodeficient
Term
What is allelic exclusion in the context of heavy chain formation?
Definition
DJ is rearranged on both chromosomes and then triggers rearrangment of VDJ first on one chromosome then another. Allelic exclusion is when there is a successful VDJ arrangment on one chromosome that stops the VDJ rearrangment on the second chromosome
Term
T/F If the DJ rearrangement is unsuccessful, the B cell with undergo apoptosis before it has chance to make a B cell.
Definition
FALSE, if the VDJ rearrangment is unsuccessful the B cell ALWAYS undergos apoptosis AFTER VDJ is made
Term
What are surrogate light chains?
Definition
proteins that mimic light chains and can combine to heavy chains. This makes sure that pro B cell has made a heavy chain able to combine with an Ig light chain
Term
Which genes encode the surrogate light chain?
Definition
VpreB encodes the variable region and "lambda"5 encodes the contant region (controlled by E2A and EBF
Term
What is the pre B cell receptor?
Definition
u chains that assemble with surrogate light chain and other factors. Successful assembly stops signal for heavy chain rearrangment
Term
How does the pre B cell stop heavy chain rearrangment from occuring?
Definition
stops transcription of RAG genes, degrades RAG proteins, and reorganizes chromatin structure
Term
Why is it adventageous for a B cell to exhibit allelic exclusion and have all of its immunoglobulins identical?
Definition
binds with antigens with high avidity
Term
How do some B cells have identical heavy chains but different light chains? coincidence?
Definition
pre B cells go through rounds of division before RAG genes are turned back on and light chain is rearranged
Term
What series of steps must occur for a light chain rearrangment to be unsuccessful and cause apoptosis?
Definition
kappa gene on first chromosome unsuccessful -> kappa gene on second chromosome unsuccessful -> lambda on first unsuccessful -> lambda gene on second unsuccessful -> apoptosis
Term
Why is it adventageous to have genes for both kappa and lambda when they are functionally identical?
Definition
increases sucess rate of rearranging a good light chain to 85%
Term
T/F One gene for heavy chain can be rearranged multiple times until a succesful chain is made.
Definition
FALSE, this only happens in light chains
Term
What halts light chain rearrangment once a successful light chain has been made?
Definition
light chain assembles with u to form igM and then assembles with cofactors to form the B cell receptor. B cell receptor is transported to cell surface and halts further gene rearrangement
Term
What must a B cell have to "pass" the two "checkpoints"?
Definition
successful heavy chain/pre B cell receptor and successful light chain/B cell receptor
Term
What is x linked agammaglobulinemia?
Definition
pts lack a functional Bruton's tyrosine kinase (Btk) gene so there are no circulating B cells and no Ab. Immune deficiency against extracellular and pyogenic pathogens
Term
Tonsils are mostly made up of...
Definition
B cells (80-90%)
Term
How do B cell translocations cause cancer?
Definition
protooncogene is translocated accidentally to Ig gene and transcribed becoming an oncogene
Term
What causes Burkitt's lymphoma?
Definition
Myc gene (which regulates the cell cycle) switches places with the Ig gene
Term
Name the only B cell that expresses CD 5.
Definition
B-1 cell
Term
Why do B-1 cells have restricted antigenic repertoires?
Definition
they are produced prenatally when TdT is not expressed. Therefore no N nucleotides and less diversity
Term
On what cell would you find low affinity, poly reactive antibodies that bind to carbohydrate antigens?
Definition
B-1
Term
What keeps up the B-1 cell population once the bone marrow stops making them?
Definition
they self renew or divide
Term
What causes most cases of chronic lymphocytic leukemia?
Definition
B-1 cells
Term
Why are other B cells monospecific while B-1 cells are polyspecific?
Definition
B cells need to have high affinity for when they undergo clonal expansion
Term
Self tolerance
Definition
when B cells do not react with self antigen
Term
When do B cells finally begin to express IgM and IgD?
Definition
when they enter the blood stream there is alternative mRNA splicing that allows expression of IgM and IgD
Term
What happens to B cells that bind a self antigen in the bone marrow?
Definition
can undergo further light chain rearrangement. surface IgM is reduced and RAG expression continues
Term
What is clonal deletion?
Definition
when a B cell keeps recognizing self antigens until no more light chain rearrangements are possible and cell undergoes apoptosis
Term
What does univalent mean?
Definition
there is only one epitope
Term
What is anergy?
Definition
when a B cell can bind to univalent self antigen. B cell makes the nonfunctional IgM receptor so it is not activated when it binds to self antigen in peripheral circulation. Cell dies in 1-5 days
Term
What is the normal half life of mature B cells?
Definition
40 days
Term
Where is central tolerance of B cells achieved?
Definition
primary lymphoid organ--bone marrow
Term
What is peripheral tolerance?
Definition
Tolerance induced outside of primary lymphoid organ (bone marrow). Circulating B cells taht encounter self antigen soon after hitting perphery are rendered anergic or die via apoptosis
Term
When is an immature B cell said to be mature?
Definition
when it enters secondary lymphoid tissue
Term
B cell survival in the periphery depends on...
Definition
regular passage through primary follicles of 2ndary lymphoid tissue. IF they meet antigen they are detained in the T cell area and signaled to proliferate and differentiate
Term
After a primary immune response subsides, memory b cells are made from...
Definition
germinal center B cells
Term
Hodgkin's lymphoma is due to uncontrolled growth of...
Definition
germinal center B cell in the periphery
Term
Multiple myeloma
Definition
uncontrolled growth of plasma cells in the bone marrow that secrete monoclonal immunoglobulin. Cause tumors in bone that enlarge and cause erosions in the bone.
Term
What happens if a naive B cell doesn't encounter an antigen?
Definition
it dies quickly (within weeks)
Term
T/F Plasma cells both secrete and express surface Ig.
Definition
FALSE, they only secrete it
Term
T/F Plasma cells both secrete and express surface Ig.
Definition
FALSE, they only secrete it
Term
T/F Plasma cells both secrete and express surface Ig.
Definition
FALSE, they only secrete it
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