BIOL 435 Ch. 11 p.1 (B-Cell Activation, etc.) Flashcards
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 Ag receptor as the original
2 B-cell responses elicited by distinct Ag types
- T-dependent (TD) responses
- T-independent (TI) responses
TD responses
- require help from T-cells
- are typically generated upon recognition of protein Ag
TI responses
- do not require T-cell help
- generated upon exposure to multivalent/polymerized Ag
TI-1 Ag
-binds to B-cell through PRRs and mIgs
TI-2 Ag
-cross-link large numbers of BCRs
TD B-cell response
- B-cells bind Ag via BCR
- induces initial activation and proliferation events
- some Ag is internalized, processed, and presented with MHC II
- TH cells provide conditions for differentiation and memory cell production
proliferation
-induces formation of germinal centres in lymph nodes/spleen
B-cells differentiate into 3 pathways
- Form a primary focus of Ab-secreting plasma cells
- IgM-bearning memory cell
- Enter germinal centre-differentiate
small soluble Ag
-acquired from lymphatic circulation by follicular B-cells
larger Ag
- captured by subscapsular sinus macrophages
- handed off to B-cells in the follicles
FDCs
- follicular dendritic cells
- serve as Ag concentration site for future selection and differentiation
BCRs cluster upon Ag binding
- molecules move into lipid rafts
- allows association of BCR ITAM signalling molecules triggering B-cell sigalling
- involves a series of SMAC-integrin-actin interactions
SMAC
-supramolecular activation cluster
B-cell signal transduction cascade
-due to Ag binding to BCR
-signalsome formation and ITAM phosphorylation
-3 co-receptors propagate Ag-BCR signals
>CD19, CD21, CD81
*leads to survial, proliferation and differentiation of the B-cell
CD21
-binds to complement fragment C3d enhancing Ag signalling
Ag can be endocytosed
- once bound to BCR
1. Ag cleaved from surface of APC by B-cell derived lysosomal proteases
2. Ag then processed via the exogenous presentation pathway and presented in MHC II
actomyosin fibers of B-cell
-exert a pulling force on BCR that pulls Ag from APC
Ab-forming cells in primary foci
- no somatic hypermutation
- provide high quantities of specific Abs early (5-6days) in immune response
- secretede IgM and IgG reduce microbial numbers
initiate germinal centre
- require CD40/CD40L interactions between B/T cells
- consist of dividing B-cells, FDC, TFH cells and macrophages: forming dark and light zones
dark zone
- densely packed with proliferating B-cells
- location of somatic hypermutation
light zone
- B cells interact with TFH cells and FDCs
- B-cells bearing high-affinity, mutated BCR are selected
what occurs in germinal centre?
-B-cell proliferate
-somatic hypermutation
>Ig variable regions undergo extremely high rates of mutation (1/1000bp/generation)
-new BCRs are tested
BCRs tested
- BCRs with higher affinity are selected for=proliferate
- BCRS with lower affinity or none=die by apoptosis
somatic hypermutation (SHM)
-produces individual point mutations in Ig H- and L- chain rearrangements
>mutations increase over time and with repeated exposures
>followed by affinity selection result in increased infinity for Ag over time
activated-induced deaminase (AID)
-mediated SHM
-enzyme expressed with DNA pol
-breaks DNA, making it need to be repaired
>not repaired well
-also class switch recombination
mutational apparatus targetting
- mutational hot spots are sequence motifs far more likely to be targeted
- mutations are prevented in non-Ig areas
