- Most b-cells screw it up and don't get out - what's the percentage chief?
What entails the selection of multiple germline genes (1st way)?
What entails H-L chain combinations (2nd way)?
- LOOK AT PICTURES IN IPAD FOR MORE DETAIL ON WAYS 1 and 3
- choosing VDJ segments (each of which has a different type) for heavy chain and VJ for light (only if both of these chains work will the b cell leave the bone marrow)
- heavy chain rearranges independenty of light chain - get various specificity by combining different H and L chains (each with their own variable region rearrangements)
(Antibodies - Allelic Exclusion) - the 5th way
- Rearrangement of the antibody gene DNA in a random event which occurs on ____ chromosome(s) for each each light or heavy chains. This is called _____.
What does allelic exclusion assure?
Does it occur for heavy or light chains?
So for example you have a yellow bunny mating with a blue bunny - their offspring can make either blue or yellow - but for each b cell it only chooses one - doesn't mix them up - thats allelic exclusion
- one, allelic exclusion
- That each individual B cell generates only a single antibody molecule rather thatn expressing the genes from both chromosomes.
Why don't you want a b cell with two different antibodies (blue AND yellow?
- you want to to have high avidity (strong binding) - if you have mutliple antibodies you have low avidity and therefore weaker binding
(Rearrangement of Antibody Variable Region Genes)
- The _____ chain gene rearranges first, followed by _____.
- If the first splice even fails, the chromosome may ______.
- Does choice of heavy chain VDJ regions influence choice of light chain V and J?
- heavy, light chain
- attempt to splice further down the gene cluster
- _____ proteins/enzymes recognize conserved sequences __________, bend the _______ such that the proteins interact, and _______ the intervening DNA sequences. Animals defincient in Rag activity are _______.
What are the circular structures calle dthat arve cleaved out?
What do the RAGs recognize on each end?
- RAG (recombination activiated genes), flanking each gene segment, DNA strand, cleave out, severely immunocompromised.
Because they don't rearrange B and T cell receptors
- signal joints
- RSS, recombination signal sequence
(Expression of surface Ig)
- B cells develop in the ____ and are released with rearranged __ genes.
Which two antibodies are found on mature B cells released from the marrow?
- Rearrangment occurs in the ____ of Ag
- bone marrow, Ig
- IgM and IgD
Why is IgM the first antibody produced by B cells?
- IgD is also found on the surface of newly formed B cells due to a ___________
- look at picture - recognize that antigen a goes up really fast the second time cuase it has already seen it once
- it is encoded immediately adjacent to the VDJ genes
- mRNA splicing artifact
- What does antibody RNA code for that allows it to lodge itself into membrane
- Which is produced more IgM or IgD?
- Will the binding pocket be different if IgD is made?
- transmembrane regions
- much more IgM
- no it will be identical
What will happen to antibodies if they bind to self-antigen in the bone marrow? What is this called?
What if there is no self-reaction?
- they will be deleted, tolerance
- will be released from bone marrow
- B cells initially mature in the _____, in the _____ of specific antigenic stimulation
- Where do they go after this?
- B cells that encounter Ag (and ____ help) form foci called ______ that contain proliferating B cells\
- What are b cells called that leave the germinal center, reenter circulation, and secrete Ab called? Where do they sometimes reside?
Where do isotype switching and somatic hypermutation occur? follwoing what?
- bone marrow, absence
- secondary lymphoid tissues - lymph nodes, tonsils, spleen, and Peyer's patches
- T cell, germinal centers
- plasma cells, bone marrow and spleen
- in the periphery, specific antigen stimulation
How long will mature be cell live if i doesn't get into secondary lymphoid tissue?
How long if it gets into there (but has no antigen interaticeion)
- Mouse bone marrow produces 10*10^6 mature b cells a day - level in periphery stays constant due to cell death. Why does it stay level (3 reasons)
- 2-3 days
- 3-8 weeks
- natural turnover, removal of cells that bind self too strongly, or those that fail to enter lymphoid tissue
What happens if a plasma cell receives further activation?
- results in isotype swithcing to secrete IgG or IgA
(Late B Stage Cell Development)
- Exposure to antigen in the periphery results in
- activation and cell division
- differentiation into _____
- _______ and ______ (introduces AA changes)
- Selection for receptor specificity with greater affinity (_______)
- Differention into _____
___ activation of B cells and subsequent changes in
DNA (somatic hypermutation and isotype switching) or
RNA processing (secretion of antibody) in the periphery
require exposure to antigen (except for gene conversion
- plasma cells
- class swithcing, somatic hypermutation
- affinity maturation
- memory B cells
(Germinal center formation)
Germinal centers are specialized areas of _______. If stimulated by _____, the B cells will multiply and start to secrete IgM. They will also undergo ______ and _____ for antigen binding sites in these sites.
Where do Plasma cells migrate to?
How about memory B cells?
- secondary lymphoid organs, antigen specific T cells, somatic hypermutation, selection
- all the other lymphoid organs
- continual re-circulation, bone marrow is popular spot - can live a long time (years)
- What brings antigen into the lympphoid organs to interact with T-cells and B cells?
- Which t cells are especially helpful to the replication B cells?
- dendritic cells (after phagocytosing something)
- TH2 (t helper 2)
- What are the first things that happen following B cell activation?
- what happens to switch the IgM from membrance to secretory?
- proliferation and conversion to secretory IgM (plasma cell)
- RNA splicing, the membrane binding portions of the code are treated as introns and the S (secretory portion) get spliced in