Lymphocyte Development Flashcards
where does B cell development occur?
surface of bone marrow stromal cells
what is the survival signal in lymphocytes?
IL-7
what genes are part of the Heavy chain of BCR?
VDJ
what genes are part of light chain of BCR?
VJ
which chains arrange first in BCR assembly
heavy chain variable regions first
what directs recombination of the VDJ gene segments in the heavy chain?
recombination recognition sequences (RSS)
what does RAG complex do?
cleaves the RRS, recombines the gene segments, and ligates the new segments
what is somatic recombination?
during B cell development, areas of VDJ are cut and respliced by DNA recombination
what triggers the continuation of somatic recombination?
the successful rearrangement of D-J triggers V-DJ rearrangement
what is a pre-B cell?
VDJ of heavy chain has been rearranged, has partial BCR
what is allelic exclusion?
only 1 H chain and 1 L chain can be expressed, and the other chromosome locus undergoes epigenetic silencing FOREVER!!!!!!
what occurs once H chain is successfully rearranged?
- other chromosome undergoes epigenetic silencing
- RAG complex is degraded
- RAG1 and RAG2 transcription stops
- large pre-B cells divide to small Pre-B cells and RAG genes are reactivated to produce new RAG complexes for light chain rearrangement
what has to occur to result in BCR expression?
successful V-J rearrangement
what occurs if kappa L chain genes fail to rearrange?
lambda Light chains attempt to rearrange
what gives additional diversity in the Ag binding site of BCR?
addition of random nucleotides at coding joints by TdT ((terminal deoxynucleotidyl transferase)
what occurs if either the H or L chains are not produced?
apoptosis
describe circulation of B cells after BCR is made
- self reactive B cells are removed (negative selection)
- IgM+ immature B cells leave the bone and go to spleen (positive selection)
- immature B cells access lymph nodes through the high endothelial vessels to become mature B cells
what does travel through lymph nodes do to the B cell?
interaction with follicular dendritic cells and cytokines drives maturation (both IgD and IgM expression)
how do B cells express both IgM and IgD constant regions
coexpression of IgD and IgM is possible by mRNA alternate splicing
where do T cells develop
TCR
thymus
what is important about the blood thymus barrier
keeps the environment clear of entering Ag so that T cells can be selected that don’t respond to self
what makes up the blood thymus barrier
CTEC and capillary endothelial cell basal lamina, with macrophages between the layers
what resides in the thymus cortex?
- T cells
- Cortical thymic epithelial cells (CTEC) assist in selecting functional T cells - have MHC I and II that interact with T cells)
- macrophages
- blood vessels
what resides in the thymus medulla?
- T cells (not as many)
- medullary thymic epithelial cells (elimination of self reactive t cells) (negative selection)
- macrophages
- dendritic cells to activate Tcells
- hassalls corpuscles
what T cell development step occurs in the thymic subcapsular layer?
double negative (CD4- CD8-_ T cells (Pro t cells) differentiate into pre-T cells expressing 1 rearranged chain of the TCR (beta chain)
what is double negative ?
pro-t cell does not have CD4 or CD8 expression
what constitutes a pro-T cell?
no CD4 or CD8 expression, no TCR
what constitutes a pre-T cell
expresses one rearranged chain of TCR (BETA CHAIN)
what TCR chain genes rearrange first?
beta chain genes
what promotes alpha chain rearrangement?
successful beta chain rearrangement
what does successful rearrangement of both beta and alpha chains trigger?
induces gene expression of BOTH CD4 and CD8 = double positive T cells
where do double positive cells occur?
cortex of thymus
where does positive selection occur?
cortex
what cells are important for positive selection?
CTEC
how are DP T cells differentiated to CD4 or CD8?
DP T cells engage CTEC to determine CD4 or CD8, and a significant number of DP T cells apoptose
where do differentiated T cells undergo negative selection?
thymic medulla
what occurs in the SP (specific) T cells once they travel into the medulla?
TCR signaling molecules are expressed, so they can form response to recognized Ag; they encounter MTEC and DC
what does MTEC do?
able to produce most of the protein/peptides (SELF ANTIGENS) found throughout body system – aka presents self antigens to Tcells to ensure they arent self reactive
what do hassal’s corpuscles do?
produce TSLP which matures the DC in the medulla so they can better present peptides to SP T cells
what occurs to SP T cells that bind strongly to self Ag?
apoptosis (negative selection)
what occurs to SP T cells that bind moderately to self Ag?
survive
what are the surviving CD4 and CD8 T cells called in the medulla?
naive and mature
what does CCR7 signal for?
migration to the secondary lymphoid organs
