B Cell Activation

Question 1

BCR Mech of B Cell Activation

Answer 1

Repetitive Ags bind BCRs and cause crosslinking/clustering of Igalpha/betas
Src family of kinases can now associated ITAM residues on Igalpha/betas
Syk family of kinases bind phosphorylated Tyrs and self-phosphorylate to activate signaling cascade

Question 2

Costimulatory Mech of B Cell Activation

Answer 2

C3d on path binds CR2/CD19/CD81 on Bcell
This complex in close association with BCR complex, so Src phosphoryaltes ITAM on C3d
Amplifed signal

Question 3

Mitogen Signaling of B Cell Activation Example

Answer 3

CD14 binds LBP binds LPS on path, causing increased activation signal

Question 4

Post-Syk Mech of B Cell Activation

Answer 4

Scaffold BLNK (with Btk associated) holds kinases together to continue signaling. PI3K generates 2nd messengers like Ca and DAG to activate TFs to cause differentiation and proliferation

Question 5

General Path of B Cells in LNs

Answer 5

Enter in HEVs in T cell area. If don’t encounter Ag; recirculate. May encounter Ag and present to TH2 cells, already activated from dendritic cells. Get activated and move to germinal centers in follicles in outside B cell area. Once differentiated, leave from efferent lymphatics and eventually go to bone marrow to produce Abs (or recirculate if memory cells)

Question 6

2.3 Kinds of Interactions w/ Ts and Bs

Answer 6

Physical - CD40L on T (stimulated by APC binding) binds CD40 on B
Secreted - Cytokines from T activate. IL-4 and 10 are growth/survival factors for proliferation, and IL-6 differentiated it into a plasma cell

Question 7

4 Isotype Directions from Cytokines

Answer 7

IL-4 - IgG, IgE
TGFbeta + IL-5 - IgA
TGFbeta - IgG
IFNgamma - IgG

Question 8

TH1 4 Roles

Answer 8

Make IL-2 and IFNgamma
Stimulate IgG production
Promote CTL response
Activate Macs (IFNgamma)

Question 9

TH2 4 Roles

Answer 9

Release IL-2,5,10 and TGFbeta
Stimulate IgG, A, and E production
So important in secretory immunity (A) and allergies (E)

Question 10

5 Main Actions in Germinal Centers

Answer 10

Bs proliferate
Class switch
SHM of V regions
Selection based on affinity
Bs become memory cells

Question 11

Germinal Center Structures (3)

Answer 11

Centroblasts - dark, dense where proliferation occurs
Centrocytes - lighter area of daughter cells
Follicular dendritic cells (FDC) - in centrocytes, present Ag in native form to Bs

Question 12

Germinal Center Mechanism of B Cell Maturation

Answer 12

Bs proliferate and undergo SHM of V region. Then they bind iccosomes via Ag-BCR interactions and receive further Th signaling to produce Bcl-x, necessary for survival. Thus only strongest affinity variants outcompete and survive.

Question 13

Iccosomes

Answer 13

Shed native Ag/Ab complexes from FDCs that B cells bind in GC via BCR-Ag interactions

Question 14

Plasma Cell and Memory B Terminal Differentiation Difference

Answer 14

Plasmas are terminally differentiated, meaning they are factories which need no further stimulation and cannot undergo anymore SHM or class switch. Memory cells can be stimulated for both of these things so they can further improve