What are the early checkpoints in B-cell development?
Pre-B-cell receptor: Selects for functional heavy chains (rearrange D-J regions, then V-DJ regions)
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.
How do B1 and B2 cells differ?
What do central and peripheral tolerance accomplish, and where do they do it?
Central and peripheral tolerance eliminate self-reactive B cells.
Central tolerance occurs in the bone marrow.
Peripheral tolerance occurs AFTER B-cell development.
What is receptor editing in B cells?
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.
What are the stages of B-cell development that take place in the bone marrow?
What are the stages of B-cell development that take place when the B cells leave the bone marrow?
What is the structure of the B-cell co-receptor?
Complex of 3 proteins:
- Complement receptor 2 (CR2/CD21) recognizes iC3b and C3D
- CD19 protein, signaling chain
- CD81, function unknown
How and why do B cells interact with T cells?
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
What are plasma cells?
Essentially, long-lived antibody factories. They are a differentiated form of B cells that secrete Ig at a high rate.
What are memory cells?
Rare, resting, long-lived cells, with unique properties. Typically class-switched cells that produce high-affinity antibodies following secondary infection.