61-Mature B Cell Responses Flashcards
basic signals required for b cell activation
recognition and binding of Ag BCR clustering signal 1-BCR signaling cascade, activation signal 2-co stimulation, survival signal 3-cytokine stimuli, expansion and differentiation
BCR structure
BCR-Ag binding site, transmembrane, no signaling ability
CD79 a/b
adapter molecules
connect surface Ig to intracellular signaling pathway
ITAM
tyrosine target that gets phosphorylated to attract signal transduction
CD19, CD21, CD81
coreceptor molecules, amplify CD79a/b
binding and clustering
Ag binds to BCR, BCR clusters which leads to activation of signal transduction cascade initiated by tyrosine motifs
TI Ags
display epitopes recognized by BCR
composed of lipid or carb
activate innate immunity (pattern recognition receptors, complement)
activate B cells
TD Ags
display epitopes recognized by BCR
composed of protein
DO NOT activate innate immunity
requires CD4 T helper to provide signals 2 and 3
Activation of B cells by TI
signal 1- binding, clustering, signal transduction
signal 2- costimulation from innate signals (TLR, PAMPs, complement)
signal 3- cytokines for expansion and differentiation from innate or T cells (DC, macrophages, neutrophils, NK cells)
Marginal zone B cells
TI antigens
epitopes are lipid or carb
rapid BCR and TLR response
does not use CD4 T helper cells
Key features of TI B cell response
rapid- do not need CD4T help
Major Ab is IgM
no germinal center-plasma cells short lived, no memory b cells, TI Ab response low affinity
Activation of B cells by T cell after infection
signal 1-peptides presented in MHC class II
signal 2- follicular helper cells express CD 154 which bind CD40
signal 3- cytokines to direct CD4 to expansion and differentiation
**use t follicular helper cells for B cell
T follicular helper cell
ability to enter B cell follicles and provide signals 2 and 3 to b cells
CD 154
expressed by activated T helper cells, ligand for CD 40
function of dendritic cells in B cell activation
bring Ag into B cell follicles
epitopes recognized by B cells
Ags bound by BCR-signal cascade initiated by crosslinking and CD79
Ag processed and presented in MHC
CD40
constitutive expression on surface of B cells
movement of T and B cells to border
after activation the cells coexpress CCR7 and CXCR5 to force movement to border
differentiation at T cell zone
1 subset quickly differentiates into antibody secreting cells (plasma cells), short lived, quick response
1 subset migrates back to follicle to seed germinal center response (lose CCR7 and keep CXCR5)
cognate interaction
cell driven activation of B cells
Germinal center
proliferation and differentiation of activated Ag specific B cells
cells in germinal center
Ag specific B cells activated by T follicular helper cells
cells that have lost CCR7 and kept CXCR5
follicular dendritic cells
macrophages to digest apoptotic B cells
processes in germinal center
proliferation-mitotic expansion
isotype switching- change heavy chain, requires continued signals 2 and 3
affinity maturation- BCR for Ag becomes higher affinity, requires signals 2 and 3
terminal differentiation- plasma or memory cells
isotype switching
in germinal center, change heavy region selected switch regions brought into close proximity forming a loops DNA excised and discarded broken strands ligated VDJ now proximal to new constant region
somatic hypermutaion
B cells given signals by T follicular helper cells to start mutation process
nucleic acid interchanges, mutations can be progressive and accumulate
lead to altered amino acid sequence at Ag binding site