Term
| Immediate precursor to plasma cell is |
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Definition
b cell
Pro b cell then Pre-b cell (with cytoplasmic heavy chain) and then b cell..... |
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Term
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Definition
| brings some heavy chain to membrane surface and instructs cell to stop undergoing heavy chain rearrangement and then now switch to initiate light chain rearrangement (either kappa or lambda) |
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Term
| How many VDJ heavy chains made in total? |
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Definition
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Term
| how many light chains made in total? |
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Definition
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Term
| b cell has 2 options.... what are they? |
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Definition
| B cells can become both plasma cells but can also stay as an APC and it can undergo pinocytosis rather than phagocytosis (like macrophages can do) |
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Term
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Definition
| combination of molecules that immediate cleaveage of DNA, correct errors of DNA, some are housekeeping genes- serve ongoing role for protecting DNA from damage |
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Term
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Definition
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Term
| Recombinase activating genes 1 and 2 (RAG 1 and 2) |
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Definition
| these are lymphoid specific components of VDJ recombinase. In both b cells and in t cells. These 2 are lymphoid specific components of VDJ recombinase |
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Term
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Definition
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Term
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Definition
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Term
| V(h) is estimated at how many? |
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Definition
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Term
| D(h) is estimated at how many gene segments? |
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Definition
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Term
| J(h) is estimated at how many gene segments? |
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Definition
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Term
| For heavy chain, how many gene segments for each type V, D, and J? |
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Definition
V(h) is estimated at 100 gene segments
D(h) is estimated at 77 gene segments
J(h) is estimated at 6 gene segments |
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Term
| For light chain, how many gene segments for V(k) and J(k)? |
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Definition
V(k) is estimated at 35 gene segments
J(k) is estimated at 5 gene segments |
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Term
| V(k) is estimated at how many gene segments? |
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Definition
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Term
| J(k) is estimated at how many gene segments? |
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Definition
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Term
| What are the 5 main types of generating diversity? |
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Definition
1) multiple v regions of gene segments
2) combinatorial association
3) combinatorial association (protein level)
4) Junctional diversity
5) Somatic Hypermutation |
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Term
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Definition
| meaning that there are millions of combinations for immune system receptors |
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Term
| Multiple V region gene segments category of generation of diversity |
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Definition
a. The genes above are not all fully functional encoded gene
b. You need to bring in other coding elements by bringing in rearrangement from other genes |
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Term
Combinatorial Association of generation of diversity.
what are the 2 different types? |
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Definition
a.)Combination of V, D, and J segments for heavy chain
i. H=(100)(77)(6) = 16,200
ii. These give you certain number of possibilities that will lead to diversity of rearrangement
b.) Combination of V and J segments for light chain
i. L(k)=(35)(5) = 175 looking only at the kappa gene family |
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Term
| Combinatorial Association at the protein level for generation of diversity |
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Definition
Any combination of heavy chain can associate with any combo of light chains
i. 16,200 heavy chains X 175 light chains = 2.835 X 10^6 millions of possibilities for receptors for antigens |
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Term
| Junctional diversity type of generation of diversity |
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Definition
| The phenomenon by which when gene segments come together during rearrangement process, there are changes that can take place before ligation at the junctional sites |
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Term
| Junctional diversity types |
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Definition
The phenomenon by which when gene segments come together during rearrangement process, there are changes that can take place before ligation at the junctional sites
b. Means that there can be billions of combinations, any number around 10^7
i. for heavy chains you have 2 junctional sites (from D to J and from V to D)
ii. for light chain you have one junction (between V and J). |
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Term
| for heavy chain, how many junctional sites are there? |
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Definition
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Term
| for light chain, how many junctional sites are there? |
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Definition
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Term
| What mediates junctional diversity??? |
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Definition
| TERMINAL DEOXYNUCLEOTIDAL TRANSFERASE (TDT). |
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Term
| TDT (terminal deoxynucleotidal transferase) |
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Definition
| it is ON ) during immunoglobin gene rearrangement process particularly when there is heavy chain rearrangement (only when heavy chain rearrangement takes place!) adds much more diversification for heavy chain than it does for light chain. adds nucleotides at junctional site |
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Term
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Definition
This is an enzyme that randomly adds nucleotides in non-template driven fashion (randomly) at breakpoints in DNA prior to re-ligation and then DNA closes up again
- it is upregulated (expressed) principally during heavy gene rearrangement and adds nucleotides from the nucleotide pool to breakpoints of DNA in a non-template driven fashion, meaning its just randomly adding nucleotides that are present in the nucleotide pool at breakpoints of DNA; immediately upon adding nucleotides, it is a very unstable component of the system to allow the DNA to have double stranded breaks so you very quickly want to re-ligate, that’s part of the VDJ recombinase but during that window of time that this enzyme is upregulated/expressed and the DNA is now open and nucleotides can be added by that enzyme. |
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Term
| After junctional diversity takes place what is the big concern? |
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Definition
does DNA remain in frame afterward? It does not sometimes.
However now we have a mechanism to increase genetic diversity of genes. So if you add one AA then you change the entire diversity of the transcript |
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Term
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Definition
| the process by which the TDT enzyme adds AA’s at breakpoints in DNA |
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Term
| what are the antigen-independent types of generation diversity? |
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Definition
1) Multiple v region gene segments
2) combinatorial association
3) Combinatorial association (at the protein level)
4) Junctional diversity |
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Term
| What is the antigen-dependent type of generation diversity? |
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Definition
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Term
| Somatic Hypermutation type of generation diversity |
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Definition
| antibodies mutate at much higher rate, particularly ones that code for DNA variable domain (DNA for immunoglobins mutates at much higher rate more than DNA that remains in the genome because of this phenomenon) |
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Term
| This phenomenon contributes directly to affinity maturation upon repeated exposure to a particular antigen |
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Definition
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Term
| Enzyme that contributes to affinity maturation |
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Definition
| AID (activation-induced cytidine deaminase) |
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Term
| AID (activation-induced cytidine deaminase) |
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Definition
an enyme that contributes to the conversion of nucleotides normally found in DNA to nucleotides in RNA:
-conversion of uridine needs to be fixed in DNA (repair mechanism leads to errors)
-this is called the error prone repair mechanism- convert wrong nucleotide at particular site within DNA of V gene segments to the correct position, the correction mechanism is error prone). This introduces a signal point mutation. Change primary sequence of antibody that will be synthesized; that change is a random event and it increases the affinity or could give rise to weaker affinity (not a problem because there are many antibodies being made so if it is too weak it will just die from apoptosis). |
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Term
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Definition
| an antigen-dependent enyme that contributes to the conversion of nucleotides normally found in DNA to nucleotides in RNA; conversion of uridine needs to be fixed in DNA |
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Term
| B cells undergo cell division and _________ (go from 1 cell on day 1 of infection to thousands on day 5, and they can undergo ___________ cell division (a b cell can become a plasma cell through division and can also become a memory b cell |
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Definition
clonal expansion
asymmetric |
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Term
| When does the process of somatic hypermutation take place for b cell? |
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Definition
| During the stage where they are converting to memory b cells and plasma cells by clonal expansion and asymmetric cell division |
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Term
| Once b cell has _________ it can undergo somatic hypermutation mediated by AID, and activation events occur |
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Definition
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Term
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Definition
| the system tries to make sure that these are expressed the most/used during an immune response |
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Term
| Do you necessarily need mutation in order to get a high affinity clone? |
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Definition
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Term
| can you have multiple isotypes of antibodies for one cell? |
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Definition
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Term
| How do you generate the different types of isotypes in a cell? |
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Definition
| When b cell can convert to plasma cell it can decide that it doesn’t want to make one specific isotype (ex. IgM) and instead wants to make another isotype (ex. IgG) so it needs to undergo class switch recombination for that to occur(and decide to make IgG or IgA or IgE, etc) |
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Term
| what enzyme mediates both somatic hypermutation as well as class switch recombination? |
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Definition
AID
However, constraints are very different for class switch recombination in comparison to VDJ rearrangement |
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Term
| if cell binds to antigen, is this a survival signal in itself? |
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Definition
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Term
| broad overview of b cell maturation process |
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Definition
stage in b cell maturation where b cells can first express IgM as immature b cells and then go through a stage where they can mature and express both IgM and IgD
Transcribe through VDJ, then through mu, and then through delta ( and then through alternative splicing of DNA, they can either get rid of delta and keep mu or get rid of mu and keep delta)
On a mature b cell you can can either IgM OR delta receptors- post transcriptional modification |
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Term
| explain class switch thoroughly |
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Definition
We know that downstream of all the V’s all the D’s and all the J’s, after undergoing VDJ rearrangement you can then have a functional variable domain…
-the first antibody that you will make in pre-b cell is IgM and this is directly downstream of the last J segment (lets call that mu)
-4 constant domains for IgM so within that box there are a series of 4 exons and introns that define all constant domains for antibody
Downstream of mu are exons that encode for the constant domains of IgD called the delta exons
-There is a stage in b cell maturation where b cells can first express IgM as immature b cells and then go through a stage where they can mature and express both IgM and IgD
Transcribe through VDJ, then transcribe through mu, and then transcribe through delta ( and then through alternative splicing of DNA, they can either get rid of delta and keep mu or get rid of mu and keep delta) and they make either IgM Or IgD |
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Term
| on a mature b cell can you express both IgM and IgD receptors? |
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Definition
NO
You can only express IgM OR IgD receptors |
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Term
| membrane spanning domain as it related to mu allows receptors to do what? |
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Definition
| anchor into the b cell plasma membrane |
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Term
| explain monomeric versus pentameric form of IgM |
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Definition
| In monomer form as a membrane receptor for antigen, it uses the membrane spanning exon to anchor IgM in PM of developing b cells. If the b cell then becomes activated to become a plasma cell where its going to secrete IgM it splices out the mu coding element from the RNA and uses what’s called the secretory exon within the RNA to make a secreted pentameric IgM. Everything is built right into the DNA. |
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Term
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Definition
this is upstream of mu. it is used by the cell to decide whether to make IgM or IgD at the post-transcriptional level
For any of the other isotypes (IgG, IgA, or IgE you must undergo gene rearrangement for those new isotypes to be expressed) |
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Term
| name all the things downstream of Cgamma3 |
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Definition
| Cgamma3 ---> Cgamma1 (encodes constant domain for IgG1) ---> Calpha1 (encodes IgA1) ---> Cgamma2 ---> Cgamma4 (encodes IgG4)---> Cepsilon (encodes constant domains of IgE) ---> Calpha2 (encodes IgA2) |
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Term
| what is the t cell's role in class switch recombination? |
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Definition
form of membrane co-activation signaling and soluble signaling through cytokines
You need a combination of antigen as signal 1 and t cell help in form of signal 2 to induce class switch recombination. |
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Term
| why is class switch recombination important? |
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Definition
| it utilizes switch sites which are repetitive DNA elements that allow rearrangement processes to take place ; elimination of that intervening DNA through activation of Cytidine deaminase and now the plasma cell will have undergone a very important subsequent rearrangement step beyond VDJ to produce a particular isotype of antibody. |
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Term
| what happens to the genes between the two switch sites that are chosen/encoded for? |
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Definition
| Everything between the two switch sites gets lost (spliced out) and then the cell makes those respective isotypes |
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Term
| 12,23 spacer rule (aka as 1 turn, 2 turn rule) |
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Definition
gives insight to DNA contribution to gene rearrangement
one turn takes about 12 gene segments and 2 turns takes about 23 gene segments |
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