Lymphocyte Development Flashcards
What is the difference between B and T cell antigen recognition?
B cells recognize antigens without MHC binding. T cells require antigens be bound to MHC for recognition
Where are B and T cells generated? Where do they mature?
Both are generated in the bone marrow. B cells complete maturation in the bone marrow. T cells complete maturation in the thymus.
What are the stages of lymphocyte maturation?
Commitment, proliferation, antigen receptor gene rearrangement/recombination, selection of lymphocytes, and differentiation (T cells only)
What is the process by which antigen receptors obtain their diversity?
VDJ recombination
What enzymes are involved with VDJ recombination? What are their functions?
RAG 1 & 2 - VDJ recombination
TdT - junctional diversity (addition/removal of bases)
What checkpoints are involved wtih selection of lymphocytes?
Successful production of one polypeptide chain, assembly of the complete receptor, elimination of self-reactive lymphocytes
How are lymphocytes “selected?”
Lymphocytes are exposed to self-antigens. Those lymphocytes that bind to self-antigens with high affinity undergo negative selection and are destroyed. Lymphocytes that poorly bind self-antigens undergo positive selection which facilitates survival and proliferation of the lymphocyte.
What cell surface markers are expressed on all mature B cells?
BCR and CD19
Pro-B cells do not express BCR. How are they distinguished?
Expression of CD19
Describe a B cell receptor.
B cell receptors made of two polypeptides, a light and heavy chain. A constant FC region binds with phagocytes, while a variable Fab region binds antigens. The
What heavy antibody chain is always first expressed in immature B cells?
Ig Mu (IgM)
Expression of pre-BCR is the first checkpoint in B cell maturation. What is required for delivery of signals from the receptor to mediate cell survival, proliferation, and maturation?
Bruton tyrosine kinase (BTK)
What chains make up the light chains?
kappa & lambda
During the small Pre-B stage of B cell maturation, what happens to the BCR?
The heavy chain of the BCR is brought into the cytoplasm of the cell for rearrangement of the appropriate light chain.
Describe the process of B cell selection and proliferation.
In the bone marrow, immature B cells are exposed to self-antigens. If the BCR binds the antigens with high affinity, the immature B cells undergo receptor editing. If the BCR again binds strongly to the antigens, the cell undergoes apoptosis. Cells that do not bind antigens with high affinity are positively selected.
What is the final step of B cell maturation? Where does it take place?
The final step involved co-expression of IgD with IgM. This step takes place in the spleen.
Describe a T cell receptor.
T cell receptors are surface-bound and composed of one alpha and one beta chain. Each chain includes a variable antigen-binding region and constant region that is bound to the cell. Antigen presentation to a TCR requires MHC and CD4/CD8 coreceptor.
What signaling receptor is expressed on the pre-TCR that is required for proliferation and maturation?
CD3
Describe the sequential rearrangement and expression of the TCR.
The beta chain is first expressed and provides signals for survival along with CD3. Next, the alpha chain undergoes rearrangement before expression.
What is meant by double positive thymocytes?
Immature T cells express both CD4 and CD8 once the alpha and beta chains are synthesized. The immature T cells remain double positive until the end of antigen-induced selection.
What are differences between B and T cell selection?
B cells may undergo BCR editing if the receptor recognizes self-antigens, while T cells immediately undergo apoptosis. T cells require presented with MHC peptide complexes.
Describe the process of T cell selection.
T cell selection takes place in the medulla of the thymus. Immature T cells are presented to self-peptide-MHC complexes. Those that bind weekly are stimulated to survive. Cells that do not recognize MHC are neglected and die. Cells that bind MHC with high affinity undergo apoptosis.
How do double positive T cells come to express only CD4 or CD8?
Thymocytes that weakly recognized peptides on MHC I become CD8 T cells. Thymocytes that weekly recognized peptides on MHC II become CD4 T cells.
