chapter 11 Flashcards
All receptors on a single B cell have what type of specificity for antigen?
identical
B cells with receptors for self-antigens are deleted during ____________________________.
embryonic development
-response that require help from T cells
-typically generated upon recognition of protein Ag
T-dependent (TD)
-responses that do not require T-cell help
-generated upon exposure to multivalent/polymerized Ag
T-independent (TI)
bind to B cells through PRRs and mIgs
TI-1 Ag
cross-link large numbers of BCRs
TI-2 Ag
Describe the basics of the clonal selection hypothesis:
-each B cell bears a single type of Ig receptor
-on stimulation, each cell will create a clone of cells bearing the same antigen receptor as the original
Proliferation induces formation of _________________________in lymph nodes/spleen.
germinal centers
What provides conditions for differentiation and memory cell production?
interaction with helper T cells
Naive B cells circulating in the periphery pass through the ___________and _____________regularly, where they meet antigen
lymph nodes and spleen
Antigen recognition by mature B cells provides a _____________________
survival signal
B-cell recognition of cell-bound antigen results in _____________________.
membrane spreading
-Next, the B cell rapidly spreads over the target
membrane before contracting back
What causes clustering of B-cell receptors upon Ag binding?
-Ag binding induces conformational change in Cμ4 domain
* This causes oligomerization of Ag-bound IgM molecules in the `plane of the membrane
* The molecules move into lipid rafts of the membrane
Describe internalization induced by antigen receptor clustering:
– Once signaling begins, BCR-Ag complexes are internalized
– Internalized Ag are processed in the exogenous pathway
– Ag peptide fragments are presented in MHC class II molecules on the B-cell surface to solicit T-cell help
What happens after B cells engage their cognate T cell partners?
B cells then downregulate CCR7, leave T cell areas, and eventually enter follicles
Some activated B cells migrate into borders of T cell areas and form primary foci and differentiate into ___________________.
plamsablasts (plasma cells)
What happens when activated B cells move into B cell follicles?
-they begin to express Bcl-6 transcription factor
-they continue to differentiate with help of TFH cells
Where do plasma cells from?
within the primary focus
Ig producing machines
plasma cells
When are plasma cells found?
within the first 5-6 days of immune responses
differentiated B cells that have began to secrete antibodies, have not yet lost the capacity to proliferate, and still bear cell surface BCRS
plasmablasts
differentiated B cells that can no longer divide, bear little to no cell surface immunoglobin, and rapidly secrete large numbers of antibody molecules
plasma cells
What is required for germinal center formation?
CD40/CD40L interactions between B/T cells
-cytokines from FDCs and TFH cells stimulate proliferation further
describe the dark zone
densely packed with proliferating B cells
describe the light zone
B cells interspersed with a network of FDCs
What two extraordinary processes occur within the germinal center?
somatic hypermutation/affinity selection and Ig class switch recombination
What is somatic hypermutation (SHM)?
it produces individual point mutations in Ig variable (but not constant) regions
-followed by affinity selection
What is affinity maturation?
the increase in average antibody affinity for an antigen that occurs during the course of an immune response or in subsequent exposure to the same antigen
What is class switch recombination?
the generation of antibody genes for heavy chain isotype other than μ and δ by DNA recombination
produces opportunity for mutation by altering deoxycytidine bases
activation-induced cytidine deaminase (AID)
Recombination occurs between donor and acceptor ________________________.
switch (S) regions
What are switch regions?
-tandem repeats of short, G-rich sequences 20-80 bp long
-contain targeting sites for AID
What signals are needed for class switch recombination?
-B cells must receive costimulatory signals from CD40/CD40L to engage in CSR
-Cytokine signal determines Ig isotype
Nude mice have the Foxn1 mutation that results in athymia. They can still respond to what type of antigen with antibodies?
T-independent
typically bacterial cell-wall components, bind to innate immunity PRRs on B cells
TI-1 antigen
polymeric protein Ag and capsular polysaccharides, crosslink many mIgM BCRs
TI-2 antigen
What are the two novel subclasses of B cells that mediate the response to T-independent Ag?
B-1 B cells
Marginal zone B cells
Negative signaling through ____________________shuts down unnecessary BCR signaling.
CD22
Negative signaling through _________________ receptor inhibits B-cell
activation.
FcγRIIb
-Circulating IgG can bind this receptor and shut down B-cell
activation
How do B-10 B cells act as negative regulators?
They secrete IL-10 which shuts down inflammatory responses by T cells and APCs
