Lymphocyte Development And Antigen Receptor Gene Rearrangement Flashcards
(93 cards)
What events occur in generative lymphoid organs that result in maturation of T and B lymphocytes?
Commitment of progenitor cells to the B or T lymphoid lineage.
Proliferation of progenitors and immature lymphocytes.
Sequential and ordered rearrangement of Ag receptor genes and the expression of antigen receptor proteins.
Selection events
Differentiation of B and T cells into functionally and phenotypically distinct subpopulations.
What do pluripotent stem cells give rise to?
Distinct B and T lineages.
What do hematopoietic stem cells give rise to?
Common lymphoid progenitors (CLPs)
What do common lymphoid progenitors (CLPs) give rise to?
B cells, T cells and NK cells.
Commitment to different lineages is driven by various transcription factors.
What can pro-B cells eventually differentiate into?
Follicular B cells
Marginal zone B cells
B-1 cells
What do pro-T cells commit to?
Alpha beta T cells
Gamma delta T cells
What is the proliferation of the committed T and B cell progenitors stimulated by?
Cytokines
What is the function of proliferation?
It ensures that a large pool of progenitor cells is available for generation of a high diversity of mature lymphocytes.
What occurs when pre-Ag receptors are successfully rearranged?
It provides survival signals that select the cell.
What do stromal cells in the thymus produce?
IL-7.
This drives the proliferation fo human T cell progenitors.
What is the development of NK cells dependent on?
IL-15
What does commitment to the B or T lineage depend on?
Sequential signaling from several cell surface receptors.
What is the function of signaling?
It activates transcription factors that contribute to the commitment via induction of gene expression and rearrangmements of the Ag receptor genes.
What occurs during the development of B cells?
The Ig heavy chain locus opens up and becomes accessible to the proteins that will mediate the Ig gene rearrangement and expression.
What occurs during the development of alpha-beta T cells?
The TCR beta gene locus opens up and becomes accessible for TCR gene rearragement and expression.
What is the function of Notch-1 and GATA-3 transcription factors?
They commit developing lymphocytes to the T cell lineage.
What are the noch family of proteins?
They are cell surface molecules that are proteolytically cleaved when they interact with specific ligans on neighboring cells.
The cleaved intracellular portion of notch protein migrates to the nucleus and modulates the expression of specific target genes.
What is the function of EBF, E2A and Pax5?
They are transcription factors that induce the expression of genes required for B cell development.
EBF, E2A and Pax-5 are transcription factors that induce the expression of genes required for B cell development. What genes do they encode?
Rag-1 and Rag-2 that regulate BCR rearragement
The surrogate light chains (pre-B cell receptor)
The Ig alpha and Ig beta signalign proteins of the B cell receptor complex.
What is the result of DNA methylation on cytosine residues?
It generally silences genes.
What is the function of modifications of histone tails of nucleosomes?
They render genes either in either the active or inactive state.
Is euchromatin tightly or loosely packed?
Loosely packed.
This makes genes available to be transcribed.
What occurs as a result of modifications of the histone tails of nucleosomes?
They either render genes as active or inactive.
Active remodeling of chromatin by proteins forming the remodeling complexes can either enhance or suppress gene expression.
What are microRNAs?
A class of small noncoding RNAs that control gene expression at the post-transcriptional level by impairing translation or by promoting degradation of the target mRNA