B Cell Activation

Question 1

Three signals that make B cells more efficient APC

Answer 1

CD80/86
LFA-1
BCR-Ag

Question 2

T or F. Just like TCRs, BCRs contain cytoplasmic tails

Answer 2

F! No cytoplasmic tails but do have ITAMs for signalling

Question 3

T or F. In unstimulated B cells, the ITAM motifs in Iga and IgB are phosphorylated

Answer 3

F! they are NOT phosphorylated

Lyn or Fyn (the regulatory molecule is phosphorylated though)

Question 4

These regulatory molecules are not activated and are physically separated from the BCR

Answer 4

Src family kinases (ex. Lyn)

Question 5

describe the steps that occur during BCR stimulation

Answer 5

1. Ag induces BCR conformational change => lipid rafts
2. Iga and B chains brought closer to Lyn in lipid rafts
3. Lyn dephosphorylated in the regulatory domain (CD45)
4. Lyn autophosphorylates
5. activated Lyn phosphorylate ITAMs

Question 6

Syk binds _____ via ____ domains and is recruited to the membrane

Answer 6

ITAMs; SH2

Question 7

How is syk activated?

Answer 7

phosphorylation by Lyn

Question 8

Syk is the same as this T cell molecule

Answer 8

ZAP70

Question 9

BLNK is the same as this T cell molecule

Answer 9

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)

Question 10

this activates the PLCy pathway

Answer 10

BLNK

Question 11

what phosphorylates Btk

Answer 11

Lyn

Question 12

what does Btk phosphorylate?

Answer 12

PLCy
- enhances its enzymatic activity

Question 13

T or F. BLNK not an enzyme; just a protein that can be phosphorylated

Answer 13

T!

Question 14

B cell co-receptor complex

Answer 14

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

Question 15

what is the purpose of the B cell co-receptor complex?

Answer 15

to amplify BCR signalling

Question 16

T or F. Some B cells don’t need help (don’t always need signal 2) whereas T cells must have help

Answer 16

T!

Question 17

The interplay between B cells and Th2 cells

Answer 17

B cells present Ag to naive Th2 = ACTIVATED

ACTIVATED Th2 give B cells second signal = plasma cell

Question 18

CD40L

Answer 18

• transmembrane protein expressed by ACTIVATED Th2 cells
• signal required for affinity maturation, isotype switching, and memory B cells

Question 19

which cytokinaes are released by Th cell to provide signal 3 to B cells

Answer 19

IL-4 and 5

Question 20

IL 2,4,5,6,21

Answer 20

secreted by Th2 to promote B cell proliferation and differentiation

influences class switching

Question 21

Blimp-1

Answer 21

B-lymph-induced maturation protein 1
- transcriptional repressor critical for plasma cell differentiation
- downregulates genes in BCR signalling, Ag presentation, and proliferation

Question 22

Main difference between CD22 on B cells and CTLA-4 on T cells

Answer 22

CD22 already there whereas CTLA-4 on T cell not expressed until after 24hrs

Question 23

2 ways of shutting down activated B cell response

Answer 23

CD22 co-inhibitory receptor
negative regulation by FcyRIIb

Question 24

explain CD22

Answer 24

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

Question 25

T or F. Circulating Ag-IgG complexes reduce B cell activation

Answer 25

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