Lecture 14 - B Cell Activation and Antibody Production (part I)

Question 1

What is the difference between the Ab response of primary and secondary immune responses?

L14 S6

Answer 1

Primary:
-IgM is produced more than IgG

Secondary:
-IgG is produced more than IgM

Question 2

Differentiate between T-dependent and T-independent B cell responses.

L14 S8

Answer 2

T-dependent:

• protein Ags
• requires CD4+ T helper cells

T-independent:
-multivalent, non-protein (TI) Ag
—polysaccharides, lipids, and nucleic acids

Question 3

What are the different B cell subsets, where are they located and what is their general fate?

L14 S9

Answer 3

B-1 cells:

• located in mucosa and tissues
• produced in fetal liver
• TI pathway/multivalent Ag
• short lived, mainly IgM
• link innate and adaptive immune system

B-2 cells (follicular):

• located in spleen
• TD pathway/protein Ag
• long-lived, mostly isotype switched

Marginal zone B cells:

• located in marginal zone
• TI pathway/multivalent Ag
• short lived, mainly IgM

Question 4

What chemokine attracts circulating follicular B cells to the follicle of secondary lymphoid organs and what cells secrete this cytokine?

L14 S13

Answer 4

CXCL13 which is produced by follicular DCs

Question 5

What methods are used to deliver Ags to the follicle?

L14 S14-15

Answer 5

Typically reach LN via afferent lymphatic vessels

Small, soluble Ags can travel to the follicle and interact with B cells without assistance

Larger Ags captured by FDCs and transported to follicles

Ag-Ab complexes and microbes are captured by Mφ in subcapsular sinus and transported to follicles

Question 6

What are the molecules produced by FDCs and their function in immune response?

L14 S16

Answer 6

• secretes CXCL13 which attracts naïve B cells and T(fh) cells
• retain Ag-Ab complexes for long period of time via FcγRIIB, CR1, and CR2(CD21)
• does not express MHC class II
• does not phagocytize or process Ag

Question 7

What is BAFF and what produces it?

L14 S17

Answer 7

B cell-activating factor (TNF family)

Provides maturation and survival signal for B cells when bound to BAFF receptor

Produced by myeloid cells in lymphoid follicles and bone marrow

Question 8

What molecules/pathways are responsible for TI B cell activation?

L14 S18

Answer 8

CR2/CD21:
-C3d binds CR2/CD21 and enhances BCR signal

TLR:
-PAMP recognition by TLR stimulates proliferation and differentiation

Question 9

What is the mechanism of TD B cell activation?

L14 S20

Answer 9

Ag presentation to TCR by B cell via MHC stimulates:

• expression of CD40L on helper T cell
• production of cytokines (IL-21) by helper T cell

Question 10

How are T(fh) cells generated and what are their functions?

L14 S23-24

Answer 10

Generation:
-naïve T cell partially activated by DC and fully activate by ICOS-L on activated B cell

Express CXCR5 (CXCL13 receptor) which allows for migration to follicle

Produces IL-21 which is important for B-cell development in germinal center

Question 11

What are the regions of a germinal center and what occurs in each region?

L14 S25

Answer 11

Dark zone:
-entry point and proliferation of activated B cells

Light zone:
-B cells interact with FDCs and Ag presenting T(fh) cells where selection and BCR editing occurs

Mantle zone