B Cell Activation Flashcards
Three signals that make B cells more efficient APC
CD80/86
LFA-1
BCR-Ag
T or F. Just like TCRs, BCRs contain cytoplasmic tails
F! No cytoplasmic tails but do have ITAMs for signalling
T or F. In unstimulated B cells, the ITAM motifs in Iga and IgB are phosphorylated
F! they are NOT phosphorylated
Lyn or Fyn (the regulatory molecule is phosphorylated though)
These regulatory molecules are not activated and are physically separated from the BCR
Src family kinases (ex. Lyn)
describe the steps that occur during BCR stimulation
- Ag induces BCR conformational change => lipid rafts
- Iga and B chains brought closer to Lyn in lipid rafts
- Lyn dephosphorylated in the regulatory domain (CD45)
- Lyn autophosphorylates
- activated Lyn phosphorylate ITAMs
Syk binds _____ via ____ domains and is recruited to the membrane
ITAMs; SH2
How is syk activated?
phosphorylation by Lyn
Syk is the same as this T cell molecule
ZAP70
BLNK is the same as this T cell molecule
LAT (no enzymatic activity)
BUT…
it’s in the cytoplasm and has SH2 domains that recognize P-Tyr on ITAMs
also have Tyrosines that can be phosphorylated (other proteins & enzymes recognize this and bind)
this activates the PLCy pathway
BLNK
what phosphorylates Btk
Lyn
what does Btk phosphorylate?
PLCy
- enhances its enzymatic activity
T or F. BLNK not an enzyme; just a protein that can be phosphorylated
T!
B cell co-receptor complex
CD21 = complement receptor 2; binds C3d
CD19 = signalling subunit, recruits SH2 domain -containing signalling proteins to phosphorylated tyrosines in its intracellular tail
CD81 (TAPA-1) = complexes with integrins and provides more activation signalling
what is the purpose of the B cell co-receptor complex?
to amplify BCR signalling
T or F. Some B cells don’t need help (don’t always need signal 2) whereas T cells must have help
T!
The interplay between B cells and Th2 cells
B cells present Ag to naive Th2 = ACTIVATED
ACTIVATED Th2 give B cells second signal = plasma cell
CD40L
- transmembrane protein expressed by ACTIVATED Th2 cells
- signal required for affinity maturation, isotype switching, and memory B cells
which cytokinaes are released by Th cell to provide signal 3 to B cells
IL-4 and 5
IL 2,4,5,6,21
secreted by Th2 to promote B cell proliferation and differentiation
influences class switching
Blimp-1
B-lymph-induced maturation protein 1
- transcriptional repressor critical for plasma cell differentiation
- downregulates genes in BCR signalling, Ag presentation, and proliferation
Main difference between CD22 on B cells and CTLA-4 on T cells
CD22 already there whereas CTLA-4 on T cell not expressed until after 24hrs
2 ways of shutting down activated B cell response
CD22 co-inhibitory receptor
negative regulation by FcyRIIb
explain CD22
Lyn phosphorylates ITIMs by Lyn = SHP-1 tyrosine phosphatase comes to ITIMs to remove phosphorylation of intracellular tail
As long as there is antigen, positive signalling pathway will predominate… the deactivating pathway still happening but not quite as strong
Once antigen is lost or removed = predominant signal will be CD22
T or F. Circulating Ag-IgG complexes reduce B cell activation
T!
- Ag-IgG complexes bind to FcyRIIb on B cell surface
- cross-linking of bound Ag between BCR and FcyRIIb = closer to activated Src kinases (Lyn)
- Lyn phosphorylates ITIM motifs on FcyRIIb
- attracts phosphatases that reverse activating signals
