11 - Adapt 5: B Cell Flashcards
What parts of B & T cell development is similar
- rearrangement of gene segments
- screening processes to avoid self reactivity
- production of subsets with discrete function
B & T cell development differences - location
T cells start in bone marrow then move to thymus for positive & negative selection
B cells start in bone marrow then go through negative selection in bone marrow
Differences between B & T cells - screening processes
T cells - positive & negative
B cells - negative
B and T cell development differences - eventual outcomes of antigen receptor stimulation
T cells require presentation & differentiate into helper or killer subset
Most B cells require T cell help for activation and secrete antibodies
How many Ig receptors does each B cell have
A single type
Once the B cell binds to antigen, what happens
Each cell will create a clone of cells bearing the same Ag receptor as the original
Once the B cell undergoes antigen-dependent proliferation, what happens?
It differentiates into memory cells or plasma cells which have massive ER & Golgi on diagrams
Plasma B cells produce what
Antibodies
2 B cell responses are elicited by distinct Ag types that are
T dependent (TD) responses & T independent (TI) responses
T dependent responses depend on
Help from helper T cells
T dependent responses are usually generated upon recognition of
Protein antigen
T independent responses are generated upon exposure to
Multitalented/polymerized Ag
TI-1 Ag binds to
B cells through PRRs
TI-2 Ag binds through
Cross-link/clustering of large numbers of B cell receptors (BCR)
T dependent B cell responses - B cells bind Ag via BCR which induces
Initial activation & proliferation events & proliferation induces formation of germinal centers in lymph nodes/spleen
T dependent responses - once germinal centers are formed, what happens to the Ag?
Some Ag is internalized and processed, then presented on cell surface by MHC class 2 molecules
TD B cell responses: interaction with helper T cells provides conditions for
Differentiation and memory cell production
How many signals do B cells get (TD response)
3
Signal 1 TD B cell response
Antigen binding onto B cell
Signal 2 - TD B cell responses
Antigen is presented on MHC 2 - T cell receptor sees it and CD4 ligand engages & drives signal back into B cells. T cell then undergoes proliferation & produces cytokines
Signal 3 TD cell response
Cytokines travel back into B cell
What causes clustering of B cell receptors upon Ag binding?
Ag binding causes oligomerization of Ag bound BCR molecules in the plane of the membrane
What is an integrin
Proteins that hold cells together maintained by cytoskeleton
In TD B cell responses, Ag receptor clustering induces
Internalization and Ag presentation
TD B cell responses - once signalling begins, BCR-Ag complexes are internalized and the internalized Ag proteins are proceses in the
Exogenous pathway
TD B cell response - Ag peptide fragments are presented
In MHC 2 molecules on the B cell surface to solicit T cell help
TD B cell response - Ag engagement upregulates
B cell CD40 (transmembrane protein) to facilitate B cell - T cell interaction. This part drives signal 2 & 3
After TD antigen activation, a conventional naive B cell turns into
Antigen activated GC precursor B cell
Antigen activated GC precursor B cells undergo proliferation and SHM which means
SHM = somatic hypermutation
What happens during SHM phase
Point mutations in areas of already recombined genes which increase affinity of B cell for antigen
What zone does proliferation and somatic hypermutation happen in
Dark zone of medullary cortex of spleen
after TD antigen activation, a conventional naive B cell migrates to
A germinal centre, usually medullary cortex of spleen
After proliferation & SHM, what process does the B cell go through
Selection
During the selection process what happens
T cell help - T cell binds to B cell & antigen presented on MHC2
What zone does selection happen in
Light zone
TD B cell response- after T cell binds to B cell, which always happens in light zone, what happens?
Differentiation & CSR
TD B cell response - what is differentiation
The B cell turning into either a plasmablast or memory B cell precursor cell
TD B cell response - what is CSR
Class Switch Recombination which allows for recombining of constant region of heavy chain & converts B cell receptor from IgM to IgA, IgG,,etc
TD B cell response - the type of Ig the receptor changes to depends on the
Constant region being replaced during CSR
TD B cell response - somatic hypermutation (SHM) affinity selection occurs within the
Germinal center
SHM produces individual point mutations in
Ig heavy and light-chain rearrangements
SHM - mutations increase over time and with repeated exposures which is followed by
Affinity selection result in increased affinity for Ag over time