T & B Cell Development Flashcards
B cell life cycle: 4 basic steps
1) VJ and VDJ rearrangements (in bone marrow)
2) immunoglobulins that bind SELF proteins undergo apoptosis (in bone marrow)
3) mature B cells bind antigens and are part of the immune response (in periphery)
4) B cells continue to mature into plasma cells and memory cells, which can prevent future infection (in periphery)
steps to a functional B cell
stem cell -> PRO-B cell -> PRE-B cell -> immature B cell -> mature B cell
*heavy chains are rearranged first (in the pro B cells)
*light chains are rearranged second (in the pre B cells)
testing the rearranged heavy chain during B cell development
*pre-B cells test their newly completed heavy chains by combining with a SURROGATE LIGHT CHAIN made of 2 invariant proteins (VpreB and lamba5)
*downstream signaling of pre-B cell receptor requires Btk (Bruton’s tyrosine kinase)
*if the heavy chain functions, there is a cellular signal to occur:
1. inhibits expression of RAG-1/2 and thus blocks further rearrangement at second heavy chain locus (termed ALLELIC EXCLUSION)
2. promotes several rounds of proliferation
3. initiates light chain rearrangement
what are the 2 invariant proteins of the surrogate light chain (B cell development)
VpreB and lambda5
what is required for downstream signaling of pre-B cell receptor
Bruton’s tyrosine kinase (Btk)
how many chances do we have to get a productive rearrangement of the HEAVY chain?
2 chances (b/c we have 2 heavy chain alleles - one from each parent)
how many chances do we have to get a productive rearrangement of the LIGHT chain?
4 chances (b/c we have kappa and lambda light chain genes, which each have an allele from each parent)
how do we ensure that a new BCR does not react with self antigens?
1) immature B cells test their completed receptor in the bone marrow to see if it responds to self
2) receptor editing: if the new BCR reacts, it has more chances to make a working receptor (continued light chain rearrangement)
3) central tolerance: if all of the rearrangements produce a self-reactive antigen, the B cell undergoes apoptosis
T cell life cycle: 4 basic steps
1) the T cell rearranges its TCR (in the thymus)
2) the T cell undergoes positive and negative selection (in the thymus)
3) mature T cells are activated by foreign antigens on dendritic cells (in the periphery)
4) activated T cells proliferate and work to eliminate the infection
5) most of the T cells die after killing the infection, but some do become memory T cells
testing the rearranged beta chain during T cell development
*the newly generated beta chain of the TCR is tested with a surrogate alpha chain (invariant protein is pTalpha)
*if the beta chain is functional, then the alpha chain is rearranged
what is the invariant protein of the surrogate alpha chain (T cell development)
pTalpha
transplant rejection meds
block T-cell activation to suppress cellular immunity and reduce acute transplant rejection
what is positive and negative selection (in T cells)
unlike BCRs, TCRs need to bind to the HLA to be activated, so TCRs must have 3 components:
1) some affinity for HLA
2) affinity for a foreign antigen
3) NOT high affinity for self-peptides bound to HLA
positive selection in T cell development
*used to permit the continued development of thymocytes bearing a TCR that has some affinity for self HLA
*mediated by cortical epithelial cells
*selects for cells with TCR having affinity for self HLA
negative selection in T cell development
*the process by which thymocytes bearing a TCR with STRONG binding to self peptide-HLA complexes are DELETED
*mediated by dendritic cells and macrophages
*thymocytes are deleted that react strongly to self-peptide/HLA complexes
