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- Most b-cells screw it up and don't get out - what's the percentage chief?

- 95%


What entails the selection of multiple germline genes (1st way)?

What entails H-L chain combinations (2nd way)?


- 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.

- both


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

- no


- _____ 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

- absence


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