Lecture 7 Flashcards
What does a single clone of a B cell recognize?
1 antigen
What does a population of B cells recognize?
Unlimited antigens
What is the main requirement for a B cell clone?
It should not recognize self antigens
What is Ig(alpha) and Ig(beta)?
Polypeptide that allows for signaling
What is phase 1 of B cell development?
Generation of B cell in the bone marrow
-creates BCR
What is phase 2 of B cell development?
Elimination of self reactive B cells in bone barrow
-Gets rid of BCR that recognizes self antigen
In phase 1 what type of cells provide important signals/growth factors which promote B cell development?
Stromal B cells in bone marrow signal for B cell development
What are the stages of B cell development?
- Early pro-B cell–>D-J rearrangement in heavy chain
- Late pro-B cell–>V–DJ rearrangement in heavy chain
3.Large pre-B cell–>1st check point–>VDJ rearranged in heavy chain, u heavy chain, surrogate light chain, pre b cell receptor on surface, checks for functional heavy chain - Small pre B cell–>V-J rearranges in light chain, u chain in ER
2nd check point - Immature B cell–>VJ in light chain is rearranged, u heavy chain, lambda or kappa light chain, IgM
- Mature B cell–>VDJ in heavy reaaranged VJ in light chain rearranged, IgD and IgM on surface
What is Interleukin 7 and what stage of B cell development is it found in?
Interleukin 7 is made from bone marrow stromal cell that allows for survival of cell through IL-7 receptor
-Found in Late pro-B cell stage
What isotype is found in the Immature B cell stage?
IgM
What isotype is found in the mature B cell?
IgD and IgM
What is and where is the first checkpoint in phase 1 of B cell development?
Checks for functional Pre-BCR (Pre-B cells)
-checks for functional heavy chain through surrogate light chain
-Large Pre B cell stage
What is and where is the second checkpoint in phase 1 of B cell development?
Checks for functional BCR (Immature B cells)
-transition between small pre-B cell and immature B cell
What is the surrogate light chain?
Allows for heavy chain to be expressed as part of the pre-BCR
-tests if heavy chain was successfully rearranged–>checks for functionality
-Made of VpreB(mimics variable light chain) and lambda5(mimics variable heavy chain)
What is VpreB?
Polypeptide that mimics variable region of light chain of true BCR
-germline–>NOT REARRANGED
What is lambda5?
Mimics the constant region of the light chain of true BCR
-germline NOT REARRANGED
How is only 1 specificity made per B cell?
- Pre-BCR–If rearrangement if heavy chain was successful–>the presence of pre BCR sends a signal that tells stop to rearrangement of another Ig Heavy gene
- BCR–>sends a signal to pre-B cells to stop rearrangement of another light gene
What is allelic exclusion?
Allows for single specificity per B cell
-Stops rearrangement of new heavy and light genes
What do new receptors (Pre BCR and Functional BCR) send signals for?
- Stopping Ig rearrangement (Allelic exclusion)–>NO MORE RAG PROTEINS
- Proliferation (make copies of functional pre BCR and BCR)–>passed 1st & 2nd check point
- Differentiation into next stage of development–>small pre BCR or Immature B cell
In phase 2 what is negative selection and where does elimination of self-reactive B cells occur?
-Kills b cells that bind to self antigens
-In immature B cells stage
What is receptor editing?
Gives a self antigen receptor multiple chances to be fixed
-continues light chain rearrangement until correct–>becomes mature
-if not fixed then it is eliminated
What is the difference between Negative selection and receptor editing?
-Negative selection–>eliminates self antigen
-Receptor editing–>allows for new specificity for self antigen
What is X-linked Agammaglobulinemia?
Immunodeficiency that makes recipient lack B cells & immunoglobulins
-Do not have BFK–>lacks BCR signaling–>no B cells
Why are patients with XLA more susceptible to encapsulated bacteria?
-No functional B cells so cannot produce antibodies(IgG) to eliminate bacteria
How many chances does an Early pro B cell have to rearrange a useful BCR?
1
How many chances does an Late pro B cell have to rearrange a useful BCR?
2
How many chances does a Pre B cell have to rearrange a useful BCR?
4
-kappa chain is chosen over lambda chain
What does a strong signal in immature cells lead to
cell death
What does a strong signal in mature cells lead to
activation
