B Lymphocytes Flashcards
Where are B cells developed in mammals?
bone marrow
Where are B cells developed in birds?
bursa of fabricius
What are the stages of B cell development?
- Pro-B cell stage
- Pre-B cell stage
- Immature B cell stage
- T1 stage
-T2 stage
What are the stages of the Pro-B cell stage?
early and late
What happens in the early Pro-B cell stage?
- D to J heavy chain recombination
- initiation of V to DJ heavy chain recombination
What happens in the late Pro-B cell stage?
- complete V to DJ heavy chain recombination
- commitment to B cell lineage
What happens in the Pre-B cell stage?
- express a precursor BCR-m heavy chain
- proliferation occurs
- daughter cells undergo light chain recombination
- precursor B cell receptor (BCR) is no longer expressed
What happens in the Immature B cell stage?
- express BCR that is membrane-bound IgM (mIgM)
- cells undergo negative selection
- at end of immature B cell stage, these cells leave bone marrow/bursa, travel through bloodstream, enter spleen as T1 B cells (transitional)
What happens during negative selection?
- select against cells that bind self-antigen
What happens to cells that recognize self antigen?
- apoptosis or undergo receptor editing
What is receptor editing?
new V and J genes are selected for light chain of BCR
What happens during T1 stage?
- cells undergo negative selection
- cells begin to express membrane bound BCR IgD in addition to membrane bound BCR IgM
- cells express receptor for B cell activating factor (BAFF)
What happens during T2 stage?
- cells receive BAFF signaling
- cells receive survival signals through mIgM and mIgD
What happens after the T2 stage?
mature naive B cells enter circulation
What are the two types of B cell activation?
- T helper dependent activation
- T independent activation
What is the goal of B lymphocyte activation?
get plasma cells that secrete antibodies
What happens when B cells enter subcapsular sinus?
migrate to follicle in the lymph node
What do B cells encounter in the follicle?
the antigen they are specific for
Can B cells recognize free antigens?
yes
Can T cells recognize free antigens?
no
What kinds of antigens can B cells bind in the follicle?
- free floating antigen
- antigen-bound complement
- antigen bound to follicular dendritic cells
- antigen bound to subcapsular sinus macrophages
How are microclusters formed?
- when BCR binds antigen, changes in B cell membrane occur, resulting in expansion of membrane
- membrane then contracts back, leaving microclusters of BCRs on the membrane
What needs to happen if the antigen is bound to another cell?
need it to break away
How can an antigen be broken away from another cell?
2 ways
- lysosomes within the B cell can migrate to the cell membrane and release compounds that cleave the connection between the antigen and other cell
- cell membrane with polymerized actin can push against the other cell, and the force causes the other antigen to break off
What happens after BCR binds to antigen (and broken off of cell if needed)?
- B cell internalized BCR and antigen
- antigen is internalized and processed and presented on MHC-II
What happens after antigen presented on MHC-II?
the B cells move to T cell zone of lymph node
What does the B cell encounter in the T cell zone?
differentiated helper T cells
How do the B cells interact with T cells in T cell zone?
- MHC-II antigen complex on B cell binds to TCR complex on T cell
- B cells express CD80 and CD86 that bind to CD28 on T cell
- CD40 on B cell binds to CD40L on T cell
- TH cell secretes cytokines (IL 2 and IL 4)
What do the ways the B cell interacts with T cells in T cell zone result in?
all of these signals cause B cell to proliferate
What happens as the B cell proliferates after signals from T cell zone?
it loses expression of membrane bound IgD and only expresses membrane bound IgM
Where does T independent activation occur?
all in the follicle
How is T independent activation similar to T helper dependent activation?
- still get BCR binding to antigen
- B cell proliferates and loses expression of membrane bound IgD
How is T independent activation different than T helper dependent?
get crosslinking with PRR
What is crosslinking with PRR?
antigen bound to PRR and BCR, so get signaling through both
- (2 receptors bound to same thing)
What are problems with T independent activation?
- don’t generate memory
- only become plasma cells that secrete IgM
- functionally limited
Where do B cells go after activation?
T-B border
What happens at the T-B border?
- some cells continue proliferation and become primary focus
- remainder of B cells go back into follicle and become more antigen specific by becoming germinal center
What happens to cells that become primary focus?
- remain in T-B border and differentiate into plasma cells
What do plasma cells from primary focus secrete?
IgM
What happens after cells become plasma cells?
leave lymph node and go to fight infection
What are germinal centers highly susceptible to?
apoptosis, so require survival signals from T(FH) cells to stay alive
What does the germinal center develop into?
dark and light zone
What happens in the dark zone?
- proliferation of B cells
- somatic hypermutation occurs
What is somatic hypermutation?
- an attempt to increase affinity of BCR for antigen
- activation of activation induced cytidine deaminase (AID) which replaces a cytidine with a uridine, creating a U-G mismatch
In what ways can a U-G mismatch be fixed?
- replace U with C and have C-G again
- replace U-G with A-T
- remove U and fill gap with any nucleotide
- excise larger stretch of DNA and fill gap
What happens in the light zone?
B cells undergo selection which tests BCR receptor affinity for antigen
How is BCR receptor affinity for antigen tested in light zone?
BCR binds antigen on follicular dendritic cells, internalizes the antigen, and presents it on MHC-II
- if no longer specific for antigen, undergoes apoptosisW
What happens in the light zone if the cell is able to present antigen?
receive survival signals from T(FH) cells
What signals do cells presenting antigen receive in light zone?
- MHC-II/antigen binds TCR complex of TFH cell
- CD40 on B cell binds CD40L on TFH cell
What happens to the B cells that survive in the light zone?
can undergo class switch recombination
What is class switch recombination?
- cytokine signals result in activation of AID
- AID creates double stranded breaks in switch regions of heavy chain class genes
- this cuts out heavy class genes
Do B cells stay in either dark or light zone?
no, they circulate between
What eventually happens to cells in the light zone?
differentiate into memory cells or plasmablasts
What happens after cells differentiate into plasmablasts?
leave lymph node and become plasma cells that secrete antibody
How are Fc receptors diverse?
- bind to different antibody classes
- expressed by different cells
- signal differently
What do Fc receptors allow?
allow innate immune cells to be antigen specific
Where are Fc receptors found?
innate immune cells
What binds to the Fc receptor?
the Fc portion of the antibody
When does signaling through Fc occur?
only when antigen is bound to Fab part of antibody
What are the different functions of antibodies?
- neutralizing agents
- agglutination
- opsonization
- complement activation
- antibody-dependent cell-mediated cytotoxicity
- antibody-activated degranulation
What do neutralizing agents do?
- locks pathogen into past cells
- antibody binds to viral proteins that would bind to cell membranes and give the virus entry to the cell
- antibody binds to viral proteins, prevents virus from entering the cell
What is agglutination?
the clumping of antigen using antibodies, making it harder to infect the cell
How does agglutination occur?
multiple antibodies bind to many pathogens and cause a cluster of pathogens bound to antibodies
What is opsonization?
marking antigen for phagocytosis
How does opsonization occur?
antibody Fc binds to Fc receptor on phagocytic cell, induces phagocytosis
- phagocytic cell then engulfs antigen and antibody complex
How does complement activation occur?
antibody bound to antigen, antibody then binds to complement initiator proteins, which initiates activation of complement via classical pathway
How does antibody-activated degranulation occur?
antibody binds to antigen, which then binds to Fc receptor on granulocytes which then causes degranulation to happen
Can IgM binds Fc?
no because expressed an pentameter
What functions can IgM perform?
neutralization and agglutination
Is IgM as antigen specific as other classes? Why or why not?
no because hasnt undergone somatic hypermutation
What functions is IgG good at?
opsonization and ADCC and activate complement
What is IgA secreted as in blood?
monomer
What is IgA secreted in the blood good at?
ADCC
What is IgA secreted as in bodily secretions?
dimer
What functions is IgA effective at in bodily secretions?
neutralization and agglutination
What is IgE effective at?
deglutination