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what are the six functional phases of B-cell development?
Repertoire assembly, Negative selection, Positive selection, Searching for infection, finding infection and attacking infection.
Where do the phases of B cell development occur?
The first three phases occur in the bone marrow, and the last three occur in secondary lymphoid tissues.
Which cells stimulate B-cell development in the bone marrow?
Bone marrow stromal cells
What is the role of the pre-B-cell receptor?
It monitors the quality of the immunoglobulin heavy chains and halts further heavy-chain rearrangement.
What happens if a pro-B cell fails to successfully rearrange its immunoglobulin heavy-chain genes?
It undergoes apoptosis (cell death).
what are the two checkpoints during B-cell development?
The first is for heavy chain rearrangement and the second is for light-chain assembly
What process allows self-reactive B cells to avoid deletion?
Receptor editing, which changes the antigen specificity of B-cell receptors.
What is the outcome for immature B cells that recognize multivalent self-antigens?
They are retained in the bone marrow and do not continue maturation.
What types of cells do activated B cells differentiate into?
Plasma cells and memory B cells.
Which type of chromosomal translocation is commonly associated with Burkitt’s lymphoma?
Translocation between chromosomes 8 and 14, involving the MYC gene and immunoglobulin heavy-chain gene.
What is the function of the chemokine CXCL13 in B-cell maturation?
It attracts B cells to primary lymphoid follicles, where they undergo final maturation.
What is the function of the protein kinase FLT3 during B-cell development?
FLT3 is a receptor on stem cells that, when bound to FLT3 ligand, initiates differentiation into common lymphoid progenitors.
What is the first immunoglobulin expressed on the surface of immature B cells?
IgM
How do bone marrow stromal cells support early B-cell development?
They provide growth factors like IL-7 and adhesion molecules that interact with developing B cells.
What are the consequences of nonproductive rearrangements in immunoglobulin genes?
If both heavy-chain alleles rearrange unsuccessfully, the B cell dies. If the light-chain rearrangement is unsuccessful, further rearrangements may occur.
What role does the adhesion molecule VCAM-1 play in B-cell development?
It binds to the integrin VLA-4 on B cells, facilitating interactions with stromal cells that promote B-cell proliferation.
What is the difference between B-1 and B-2 cells?
B-1 cells develop during fetal life, have low diversity, and self-renew, while B-2 cells are produced throughout life and have higher diversity.
What happens to immature B cells that recognize monovalent self-antigens?
They enter a state of anergy (non-responsiveness) and do not initiate immune responses.
How do B cells enter secondary lymphoid tissues?
They enter via high endothelial venules (HEVs), attracted by chemokines like CCL19 and CCL21.
What is receptor editing in B cells?
Receptor editing is the process of continuing light chain rearrangement in self reactive B cells to alter antigen specificity and prevent autoimmunity
What is the significance of the BAFF protein in B-cell maturation?
BAFF (B-cell Activating Factor) is critical for the survival and maturation of B cells in lymphoid follicles.
At which stage does rearrangement of the light-chain genes occur?
In pre- B cells
What signals the cessation of heavy-chain gene rearrangement in developing B cells?
Successful signaling by the pre-B-cell receptor.
What are the two main functions of the surrogate light chain in the pre-B-cell receptor?
It helps test the quality of the heavy chain and triggers signaling for further development.
What type of genetic alteration is frequently associated with B-cell tumors?
Chromosomal translocations involving immunoglobulin genes
What is the role of Pax-5 in B-cell development?
Pax-5 is a transcription factor that activates genes necessary for B-cell differentiation and immunoglobulin gene rearrangement.
What are the primary differences between immature and mature B cells?
Immature B cells express IgM and are still undergoing selection processes, while mature B cells express both IgM and IgD and have completed their development.
What is the function of follicular dendritic cells (FDCs) in B-cell maturation?
they present antigens and provide survival signals necessary for the final maturation of B cells in lymphoid follicles.
What is the significance of IgM and IgD co-expression on mature B cells?
It indicates that the B cell is fully mature and capable of responding to antigens