B cell Immunity- L10 Flashcards
B cells develop in the
Bone marrow, called mature naive B cells when they leave the marrow
B cells develop from what cell with what marker?
Pluripotent hematopoietic stem cells with marker CD34
Common lymphoid progenitors have what marker?
CD34 and CD10
B-cell precursors have what markers?
CD34, CD10, CD127
Pro-B cells have what markers?
CD34, CD10, CD127, CD19
What happens in the early pro B stage?
D-J rearrangement of heavy chain
What happens in the late pro B stage?
V-DJ rearrangement of heavy chain
What happens in large pre-B cells stage?
VDJ is rearranged and mu heavy chain of Ig is made
What happens in small pre-B cell stage?
VDJ is rearranged, V-J of light chain is rearranging, and mu chain is in the ER of Ig
What happens in an immature B cell?
VCJ is rearranged, VJ is rearranged, gamma or kappa of light chain IgG is made, IgM is on surface.
What percentage of cells produce a productive heavy chain and survive to become pre-B cells?
About 50%
What region does the light chain not have?
D region
What are the two checkpoints in becoming an immature B cell?
- Pre-B cell receptor
- B cell receptor
If these aren’t met the cell will apoptose
Burkitt’s lymphoma
- Chromosomal aberration during B cell development
- MYC and Ig on chromosomes 8 and 14 respectively get translocated
B-1 cell characterstics
- Produced in fetus
- Few N regions in VDJ junctions
- Smaller V region repertoire
- Primarily located in peritoneal and pleural cavities
- Self-renewing
- More IgM than IgG
- Little somatic mutation
- Little memory development
Central tolerance
- Avoiding self
- If no reaction with a self antigen–moves to blood to express IgD and IgM
- If reaction with self the immature B cell is retained in bone marrow and RAG gene is reexpressed to try and rearrange again. Will continue rearranging until a nonself receptor is expressed.
Anergy
Interaction of immature B cells with monomeric antigen induces a state inactivity called anergy. Signaled to make IgD and become unresponsive to antigen.
B cell trafficking in the periphery
- B cell area in the cortex
- Enter through HEV
Chemokine CCL21
Attracts immature B cells to HEV and into lymph node
CCL19
Attracts B cells into lymph node
Chemokine CXCL13
Attracts B cells into the primary follicle
Follicular dendritic cells
Drive the final maturation of B cells
B cells mature where?
Germinal centers of lymph nodes
How do B cells signal?
- Cross linking of B-cell receptors by antigen
- Clustering of antigen receptors allows receptor-associated kinases to phosphorylate ITAMs
- SyK binds to doubly phosphorylated ITAMs and is activated on binding