"Microbiology/Immunology B Cell Immunity" MARY Flashcards
The life and death of the B cell has 6 phases. Explain the first 3 phases: Repertoire, Negative Selection, Positive Selection.
- Repertoire: Generation of diverse and clonally selected BCR in the bone marrow
- Negative Selection: Remove BCRs that self-respond
- Positive Selection: Some immature B cells become mature B cells in secondary lymphoid tissue
The life and death of the B cell has 6 phases. Explain the 4th to 6th phases: Searching For Infection, Finding Infection, Attacking Infection.
- Searching for Infection: self explanatory
- Finding Infection: Activation and cloning of B cells in secondary lymphoid tissues
- Attacking Infection: differentiation of plasma cells and memory B cells in secondary lymphoid tissue
When B cells exit the bone marrow, they are called:
Mature Naive B cells
At what stage is the Ig status first conferred?
Large pro-B-cell, mu heavy chain is formed
Germline means?
Not re-arranged
A B-cell at the stem cell stage has what characteristics?
H chain - still germline
L chain - still germline
No Ig status
Which chain develops first in B cell development, H, or L, an what genes does it involve?
H chain develops first, at the “early pre-B cell” stage, and begins with D-J re-arrangement
Rearrangements D-J, V-DJ happen in the development of what chain and in what cell?
B cell, H chain
begins at “early pre-B cell stage”
finished (if the cell survives) at the end of the “late pre-B cell stage”
At what stage in development of the B cell does the L chain begin to be re-arranged, and what genes do the re-arranging?
Small pre-B-cell stage, with V-J re-arrangement. No D gene in the L chain.
What are the roles Ig-beta and Ig-alpha (NOT IgA)?
They help with pre-BCR signaling, to establish whether the heavy chain (H chain) works
What is allelic exclusion?
The process by which certain genes are expressed and certain genes are silenced. It increases avidity of homogenous B cell
Receptors expressing miu and k are what Ig class? What about receptors expressing miu and lambda?
They are all IgM.
T/F: Various markers can be used to define B-cell developmental stages.
True. Some are surface markers, others, transcription factors etc.
What is the source of the problem in Burkitt’s Lymphoma?
Myc gene is translocated to Ig gene, and Ig gene gets cell regulatory influence, causing pathological proliferation.
When are B-1 cells produced?
During fetal development
When are B-2 cells produced?
After birth, as compared to B-1 cells, which are only produced during fetal development.
In terms of repertoire and variability, which cells have more, B-1 or B-2 cells?
B-2.
B-1 has more IgM and B-2 has more IgG
Negative selection, the immature B cell in the bone marrow, serves what purpose?
To test the developing B cell against self antigen
Also known as central tolerance
An immature B cell that expresses IgM and IgD, and is released from the bone marrow into the blood, has accomplished what task?
It successfully did not react to self antigen.
T/F: Immature B cells, if they sensitize to self antigen in the bone marrow, can go through rounds of self editing to try to correct the problem.
True. The developing B cell can continue to rearrange light chains.
What happens in peripheral tolerance?
Lymphocytes that recognize self antigens in peripheral tissues are shut off, sup- pressed by regulatory T lymphocytes. These cells become “anergic.”
B-cells that go through lymph nodes encounter what cell types as they experience the final stages of BCR development?
Follicular cells
Dendritic cells
B cells go into the primary lymphoid follicle, B-cell area, T-cell area, medullary cords, and leave through the efferent lymphatic vessel
Chemokines CCL21 attracts maturing B cells where?
HEV - high endothelial vessels
What attracts maturing B cells to lymph nodes?
Chemokines CCL21 and CCL19
In B cell response to an infection, where are the germinal centers of development?
Primary follicle
The plasma cells make their antibodies in the medulla.
T/F: B cell tumors can arise in any stage of development, but will not develop in the periphery–only in the bone marrow.
False, B-cell tumors can form in bone marrow and ther periphery.
These stages of B cell development happen where?
Stem cell, early pro-B cell, late pro-B cell, large pre-B cell, small pre-B cell, immature B cell.
All these stages occur in the bone marrow.
What stages of the life of a B cell occur in the secondary lymphoid organs?
Immature B cell Mature naive B cell Antigen-activated B lymphoblast Ab secreting plasma cell Memory cell
When does somatic hypermutation occur?
After antigen has activated the mature naive B cell (the “antigen activated B lymphoblast stage)
What is the general overview of B-cell trafficking in the blood?
Lymph node –> vein –> heart –> arteries –> lymph node
What are the 3 main steps in B cell signaling?
- Cross linking of BCR by antigen
- Clustering of antigen receptors allows receptor-associated kinases to phosphorylate the inner chains of the BCRS
- Syk binds to doubly phosphorylated BCRs and becomes activated.
Ultimate goal is changes in transcription
Do B cells have co-receptors?
Yes, for example CD 19, CD 81.
T/F: B-cell activation can occur independent of T-cells.
True. B-cells are cross-linked to T-cell-independent antigen, and with the B-cell co-receptors, can bypass T-cells.
How do B-cells “see” antigen?
B-cells capture and display of intact antigens by CR2 displayed on follicular dendritic cells and subscapular sinus macrophages.
What are FDCs?
Follicular dendritic cells (FDCs) are cells of the immune system found in primary and secondary lymph follicles of the B cell areas of the lymphoid tissue.
What drives B cell proliferation and differentiation?
T-cell help
Mutual antigen recognition by B and T cells (cognate interactions)
How do B cells and T cells find each other?
There is the primary follicle, and boundary region and the T-cell area. Both B and T-cells proliferate (B cells with FDCs and T-cells with dendritic cells) and then meet each other at the boundary area.
How do cytokines influence B cells?
They drive B-cell diversification, for example, IL-4 induces IgG1 and IgE but inhibits others…
IL5 augments production of IgA
IFN-gamma induces IgG3 and IgG2a but inhibits others…
TGF-beta induces IgG2a and IgA
What is the only intrinsic cell quality of plasma cells?
IgG secretion
Surface MHC Class II is found where?
On naive B cells
Where does somatic hypermutation occur?
Germinal centers, sites of intense antigen competition
