B and T cell development Flashcards
CLP
Common Lymphoid progenitor
Becomes pro-B cell if expresses EBF, E2A and pax5 or becomes T/ILC progenitor
T/ILC progenitor expresses Notch1 and GATA3 and becomes Pro-T cell or expresses Id2 and becomes ILC
Mature naive T cells
Produced in the thymus
alphabeta CD4+ T cells (Th precursors)
alphabeta CD8+ (CTL precursors)
Deltagamma T cells
DN thymocytes
CLP enters thymus from bone marrow
Express notch receptor and interact with notch ligand on thymus cells (commitment to T-cell lineage)
Thymocytes (immature) are first CD4-CD8- (DN)
DN1-4 stages of development. Proliferate and rearrange TCR beta, delta and gamma genes
DP thymocytes
Thymocytes mature to TCRgammadelta lineage if rearrange delta and gamma
Beta selection detects thymocytes that rearrange beta receptor chain. Assembles with TCR alpha chain and CD3 complex proteins.
TCR alphabeta lineage matures to double positive stage of development and TCR alpha rearrangement initiates
Positive/negative selection
pMHC is self-peptide complex expressed by thymic epithelium
High affinity TCR/pMHC interaction results in negative selection by apoptosis (clonal deletion)
Low affinity results in positive selection and maturation to single positive lineages
Majority of thymocytes do not interact with any MHC/self-peptides and die by neglect
T cell lineage commitment
Thymocytes with TCR that preferentially interact with MHCII generate continuous signal that initiates CD4+ Th cell development
Thymocytes with TCR that preferentially interacts with MHCI do not generate a continuous signal which initiates CD8+ development
Final functional maturation occurs in the peripheral lymphoid tissues
T regulatory cells
Some self reactive CD4+ T cells differentiate into regulatory cells (Treg)
Express TF FoxP3 and downregulate T cell function by cytokine deprivation, cytotoxicity, inhibitory cytokines and by inhibiting APCs
B1 cell development
Originate during foetal development
High IgM expression, low IgD expression.
Express CD5
B2 cell development
Follicular B cells. Low IgM expression, high IgD expression. Express CD19/21 and CD23
Immature B cells leave bone marrow as transitional 1 (T1) B cells
Enter spleen where IgD expression increases and become T2 cells.
T2 cells mature to FB2 or MZ cells
FB2 cells exit spleen and circulate
Marginal Zone B cells
Mature from T2 B cells
Remain in spleen and specialise for detection of blood-borne antigens
High IgM, low IgD. Express CD1 and CD19/21
B cell positive/negative selection
Positive selection for cells that form a functional BCR. Die otherwise
Immature cells with BCR specific for self-antigens in the bone marrow are deleted by apoptosis
Selection for self-tolerance also occurs in the spleen
Deletion/mutation of Foxp3
Defects in Treg cell development
Present with IPEX syndrome, manifesting as an autoimmune disorder, primarily affecting the intestines
