"Microbiology/Immunology B Cell Immunity" MARY

Question 1

The life and death of the B cell has 6 phases. Explain the first 3 phases: Repertoire, Negative Selection, Positive Selection.

Answer 1

1. Repertoire: Generation of diverse and clonally selected BCR in the bone marrow
2. Negative Selection: Remove BCRs that self-respond
3. Positive Selection: Some immature B cells become mature B cells in secondary lymphoid tissue

Question 2

The life and death of the B cell has 6 phases. Explain the 4th to 6th phases: Searching For Infection, Finding Infection, Attacking Infection.

Answer 2

1. Searching for Infection: self explanatory
2. Finding Infection: Activation and cloning of B cells in secondary lymphoid tissues
3. Attacking Infection: differentiation of plasma cells and memory B cells in secondary lymphoid tissue

Question 3

When B cells exit the bone marrow, they are called:

Answer 3

Mature Naive B cells

Question 4

At what stage is the Ig status first conferred?

Answer 4

Large pro-B-cell, mu heavy chain is formed

Question 5

Germline means?

Answer 5

Not re-arranged

Question 6

A B-cell at the stem cell stage has what characteristics?

Answer 6

H chain - still germline
L chain - still germline
No Ig status

Question 7

Which chain develops first in B cell development, H, or L, an what genes does it involve?

Answer 7

H chain develops first, at the “early pre-B cell” stage, and begins with D-J re-arrangement

Question 8

Rearrangements D-J, V-DJ happen in the development of what chain and in what cell?

Answer 8

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”

Question 9

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?

Answer 9

Small pre-B-cell stage, with V-J re-arrangement. No D gene in the L chain.

Question 10

What are the roles Ig-beta and Ig-alpha (NOT IgA)?

Answer 10

They help with pre-BCR signaling, to establish whether the heavy chain (H chain) works

Question 11

What is allelic exclusion?

Answer 11

The process by which certain genes are expressed and certain genes are silenced. It increases avidity of homogenous B cell

Question 12

Receptors expressing miu and k are what Ig class? What about receptors expressing miu and lambda?

Answer 12

They are all IgM.

Question 13

T/F: Various markers can be used to define B-cell developmental stages.

Answer 13

True. Some are surface markers, others, transcription factors etc.

Question 14

What is the source of the problem in Burkitt’s Lymphoma?

Answer 14

Myc gene is translocated to Ig gene, and Ig gene gets cell regulatory influence, causing pathological proliferation.

Question 15

When are B-1 cells produced?

Answer 15

During fetal development

Question 16

When are B-2 cells produced?

Answer 16

After birth, as compared to B-1 cells, which are only produced during fetal development.

Question 17

In terms of repertoire and variability, which cells have more, B-1 or B-2 cells?

Answer 17

B-2.

B-1 has more IgM and B-2 has more IgG

Question 18

Negative selection, the immature B cell in the bone marrow, serves what purpose?

Answer 18

To test the developing B cell against self antigen

Also known as central tolerance

Question 19

An immature B cell that expresses IgM and IgD, and is released from the bone marrow into the blood, has accomplished what task?

Answer 19

It successfully did not react to self antigen.

Question 20

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.

Answer 20

True. The developing B cell can continue to rearrange light chains.

Question 21

What happens in peripheral tolerance?

Answer 21

Lymphocytes that recognize self antigens in peripheral tissues are shut off, sup- pressed by regulatory T lymphocytes. These cells become “anergic.”

Question 22

B-cells that go through lymph nodes encounter what cell types as they experience the final stages of BCR development?

Answer 22

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

Question 23

Chemokines CCL21 attracts maturing B cells where?

Answer 23

HEV - high endothelial vessels

Question 24

What attracts maturing B cells to lymph nodes?

Answer 24

Chemokines CCL21 and CCL19

Question 25

In B cell response to an infection, where are the germinal centers of development?

Answer 25

Primary follicle

The plasma cells make their antibodies in the medulla.

Question 26

T/F: B cell tumors can arise in any stage of development, but will not develop in the periphery–only in the bone marrow.

Answer 26

False, B-cell tumors can form in bone marrow and ther periphery.

Question 27

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.

Answer 27

All these stages occur in the bone marrow.

Question 28

What stages of the life of a B cell occur in the secondary lymphoid organs?

Answer 28

Immature B cell
Mature naive B cell
Antigen-activated B lymphoblast
Ab secreting plasma cell
Memory cell

Question 29

When does somatic hypermutation occur?

Answer 29

After antigen has activated the mature naive B cell (the “antigen activated B lymphoblast stage)

Question 30

What is the general overview of B-cell trafficking in the blood?

Answer 30

Lymph node –> vein –> heart –> arteries –> lymph node

Question 31

What are the 3 main steps in B cell signaling?

Answer 31

1. Cross linking of BCR by antigen
2. Clustering of antigen receptors allows receptor-associated kinases to phosphorylate the inner chains of the BCRS
3. Syk binds to doubly phosphorylated BCRs and becomes activated.
   Ultimate goal is changes in transcription

Question 32

Do B cells have co-receptors?

Answer 32

Yes, for example CD 19, CD 81.

Question 33

T/F: B-cell activation can occur independent of T-cells.

Answer 33

True. B-cells are cross-linked to T-cell-independent antigen, and with the B-cell co-receptors, can bypass T-cells.

Question 34

How do B-cells “see” antigen?

Answer 34

B-cells capture and display of intact antigens by CR2 displayed on follicular dendritic cells and subscapular sinus macrophages.

Question 35

What are FDCs?

Answer 35

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.

Question 36

What drives B cell proliferation and differentiation?

Answer 36

T-cell help

Mutual antigen recognition by B and T cells (cognate interactions)

Question 37

How do B cells and T cells find each other?

Answer 37

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.

Question 38

How do cytokines influence B cells?

Answer 38

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

Question 39

What is the only intrinsic cell quality of plasma cells?

Answer 39

IgG secretion

Question 40

Surface MHC Class II is found where?

Answer 40

On naive B cells

Question 41

Where does somatic hypermutation occur?

Answer 41

Germinal centers, sites of intense antigen competition