2-27 B-Cell Immunity

Question 1

What are the early checkpoints in B-cell development?

Answer 1

1. Pre-B-cell receptor: Selects for functional heavy chains (rearrange D-J regions, then V-DJ regions)
2. B-cell receptor: Selects for functional light chains (rearrange κ genes on 1st, then 2nd chromosome; next, λ genes on 1st, then 2nd chromosome)

Multiple gene rearrangements can rescue cells from apoptosis.

Cells that have completed rearrangements express a functional IgM receptor on their surface.

Question 2

How do B1 and B2 cells differ?

Answer 2

Question 3

What do central and peripheral tolerance accomplish, and where do they do it?

Answer 3

Central and peripheral tolerance eliminate self-reactive B cells.

Central tolerance occurs in the bone marrow.

Peripheral tolerance occurs AFTER B-cell development.

Question 4

What is receptor editing in B cells?

Answer 4

Randomly generated B-cell receptors may bind to self-ligands, which creates a potential for self-reactivity. Re-expressing RAG genes and rearranging another light chain can modify the receptor and avoid the danger.

The alternative light chain generates a new specificity; if this does not bind to self, B-cell development continues. Receptor editing makes B-cell development more efficient.

Question 5

What are the stages of B-cell development that take place in the bone marrow?

Answer 5

Question 6

What are the stages of B-cell development that take place when the B cells leave the bone marrow?

Answer 6

Question 7

What is the structure of the B-cell co-receptor?

Answer 7

Complex of 3 proteins:

1. Complement receptor 2 (CR2/CD21) recognizes iC3b and C3D
2. CD19 protein, signaling chain
3. CD81, function unknown

Question 8

How and why do B cells interact with T cells?

Answer 8

B-cell responses to most antigens require the assistance of helper T cells, which drive B-cell proliferation and differentiation.

• B cells process antigens to peptides and present them to CD4 T cells via class II MHC
• B and T cells meet at the border of the B and T cell zones in 2° lymph tissues
• B cell must find a cognate T cell that recognizes the peptide presented
• CD4 T cells activated → produce factors that promote B-cell proliferation and differentiation
• Further B cell-T cell intrxns occur in germinal centers (GCs) → promote receptor class switching and somatic mutation
• B cells differentiate to memory cells or antibody-secreting plasma cells

Question 9

What are plasma cells?

Answer 9

Essentially, long-lived antibody factories. They are a differentiated form of B cells that secrete Ig at a high rate.

Question 10

What are memory cells?

Answer 10

Rare, resting, long-lived cells, with unique properties. Typically class-switched cells that produce high-affinity antibodies following secondary infection.