L13, B cell development and activation Flashcards
B cells migrate from … to … during development
marrow to peripheral tissues
B cell development begins where?
in the bone marrow
what are the stages of B cell development in the bone marrow?
- starts from hematopoietic stem cells
- progressively differentiate into common lymphoid progenitors (CLPs) cells
- CLPs can give rise to either B cells or T cells
- the majority of CLPs that remain in the bone marrow eventually become B cells
what two things do B cells express differently from one another during sequential development?
cell-surface receptors and adhesion molecules
what signals are received from cell-surface receptors on developing B cells?
- differentiation
- proliferation
- movement within the bone marrow environment
where do B cells complete their differentiation?
the spleen
how can stages of B cell development be defined?
by status of the BCR/Ig gene rearrangements and the expression of different markers
when do developing B cells leave the bone marrow?
once they become Mature B cells
What development occurs in the spleen?
mature B cell becomes activated via antigen stimulation, differentiation, IgM secreting plasma cells, class switching (becoming either memory B cells or Plasma cells secreting various isotyes)
What happens in the early and late pro-B cell development?
- early pro-B cell stage: DJ recombination of the heavy chain
- late pro-B cell stage: V-DJ recombination of the heavy chain
what happens in the large and small pre-B cell development?
- large pre-B cells express the pre-BCR
- small pre-B cell stage: V-J recombination of the light chain
what are the 2 Pre-B cellcheckpoints
- first checkpoint: functional pre-BCR (large pre-B)
- second checkpoint: functional BCR and self-reactivity (Immature B)
what is happening once developing B cells become immature B cells?
- express IgM at their surface and undergo negative selection
- leave the bone marrow towards the periphery and secondary lymphoid organs
what are the three possible fates during negative selection of immature B cells?
- deletion of autoreactive immature B cells
- anergic
- receptor editing
what are the three possible fates of negative selection known as?
central tolerance
what can the stages of B cell development be defined by?
- status of the BCR/Ig gene rearrangements
- expression of surface markers, notably:
B220, CD19, Il-7R
apart from differentiation, once in the spleen, immature B cells undergo what?
positive and negative selection
what are transitional B cells?
B cells undergoing either positive or negative selection
where do T1 transitional B cells undergo selection?
the periarteriolar lymphoid sheath (PALS)
BCR with high affinity for self-antigens = …
negative selection
where do T1 differentiate into T2?
in the follicle
what kind of selection do T2 B cells undergo?
positive selection
positive selection of T2 B-cells depends on what two survival signals?
- tonic signaling through the BCR
- binding of BAFF through a receptor
what do mature B cells express on their surface?
both IgM and IgD
what are the key differences between T cell and B cell development?
- development of B cells does not involve the thymus
- negative selection of B cells does not involve the expression of self-antigens in the thymus and does not involve recognition of MHC/self peptide…but both B cells and T cells bearing a self-reactive receptor are eliminated
what is T cell dependent activation?
- an antigen binds to the BCR, is internalized, and is processed to be presented to Th cells
- co-stimulatory molecules strengthen the interactions between B and T cells
- Th cells secrete cytokines that further activate B cells
What is T cell independent activation 1?
antigen binds to the BCR and others to PRR (ex. TLR)
what is T cell independent activation 2?
antigen bound to the complement protein C3d interacts with the BCR and CD21 molecules
what are the lymphoid organ regions?
T cell zone and Germinal center
what occurs in the T-cell zone?
conventional naive B cell undergoes TD antigen activation and differentiates into memory or plasma cells
what occurs in the Germinal Center?
- proliferation and somatic hypermutation in the dark zone
- selection of high-affinity, mutated, receptor-bearing B cells in the light zone
what initiates somatic hypermutation?
enzyme AID (activation-induced cytidine deaminase)
where do SHM occur in B cells? why are somatic hypermutations important?
in the variable regions of antibody-coding genes
important because they help fine-tune the binding affinity, a process called affinity maturation
where does class switching recombination (CSR) occur?
in the germinal centers after T cell-dependent antigen stimulation
in what region of the antibody genes does CSR occur in?
only the constant region
