1.04 - Lymphocyte Development I Flashcards
Describe the process of B-cell receptor light chain rearrangement and production
Germline DNA contains 4 segments: L-V—J–C
Somatic recombination joins the V & J segment in the rearranged DNA: L-VJ–C
Transcription then occurs to produce primary transcript RNA: L-VJ–C
Splicing of the RNA removes the introns and brings the L and VJ segments together as well as the VJ next to the C: LVJC
Translation of the mRNA produces the functional polypeptide chain that is sent to the cell surface
What is the function of the L segment in B cell receptor transcription?
Leader protein
Directs the protein into the cells secretory pathways and is then cleaved off.
Describe the process of B-cell receptor heavy chain rearrangement and production
Germline DNA contains 5 segments: L-V—D—J–C
The C region contains 4 exons (3 for constant region. 1 for hinge region)
Somatic recombination brings D-J segments together in rearranged DNA: L-V—DJ-C
Another stage of somatic recombination brings the V to the DJ segment: L-VDJ—C
Transcription forms primary transcript RNA: L-VDJ–C
Splicing of the introns forms mRNA: LVDJC
Translation forms the functional polypeptide chain that is sent to the cell surface
What are the features of the adaptive immune system?
Slow onset
Response is directed against specific antigens
Subsequent challenges with a specific pathogen results in a more effective immune response
What is Clonal Selection?
Antigen mediated activation and proliferation of a clone
- B cells with receptors specific for the antigen
- T cells with receptors specific for a complex of MHC and peptides derived from the antigen
What are the five antibody classes
IgG IgM IgD IgE IgA
What are the series of events in B and T lymphocyte development?
Commitment of progenitor cells to B or T cell lineage
Proliferation of progenitors and immature committed cells
Sequential and order rearrangement of antigen receptor genes and proteins
Selection of cells producing appropriate antigen receptor proteins
Elimination of cells recognising self-antigens
Differentiation of T and B cells into functionally and phenotypically distinct population
What are the three cells of the lymphoid lineage?
B Cells
T Cells
NK Cells
What are the cellular stages of B cell development?
Early pro-B cell Late pro B cell Large pre-B cell Small pre-B cell Immature B cell Mature B cell
Describe the Pro-B-Cell
Heavy chain locus rearrangement (recombination)
D-J rearrangement occurs in early pro b cell
V-DJ rearrangement occurs in late pro b cell
Production of intact heavy chain (mu (u) chain)
Removal of cells that do not produce a u chain
Describe the large pre b cell
Expression of u heavy chain (component of Pre-B-Cell receptor)
Intracellular with transient cell surface expression
Production of surrogate light chains
Provides signal that a produce rearrangement has occurred
Signals transition to small pre-b cell and onset of proliferation
One allele becomes silenced (prevent having two antigenic specificities)
Describe the small pre b cell
Rearrangement of genes at light chain locus
Light chain loci lack D segments
V-J joining
Failure to make functional light chain results in repeated rearrangements of unused V and J gene segments
Describe the immature B cell
rearrangement of heave and light chains
Expression of u chain (IgM) on the cell surface
Tested for tolerance to self antigens (bone marrow)
What are some of the outcomes for the B-Cell after development?
Lack of strong reactivity to self antigens –> leave bone marrow & differentiation to IgM & IgD mature B cell
Cell death by apoptosis
Clonal deletion: removal of cells of a particular antigen specificity from the repertoire
Receptor editing: deletion of self-reactive light chain with further gene rearrangement continuing until a non-reactive receptor is produced of V and J gene segments exhausted
Anergy: B cell can’t be activated by their specific antigen even with T cell help
