Immunology Lecture 10 Development Of B Cells

Front 1

What are the four phases of B cell development

Back 1

1. Development from stem cells in the bone marrow
2. Elimination of self-reactive cells
3. Migration to the periphery
4. Terminal antigen-stimulated differentiation into effector and memory cells

Front 2

Where do the first two phases of B cell development take place

Back 2

The bone marrow

Front 3

What is the most important aspect of the first stage of B cell development

Back 3

The stepwise process by which functional BCR/Ig genes are formed. This ensures that the B cell produces Ig of a single specificity.

Front 4

B cell interactions with the bone marrow stroma are required for what

Back 4

To maintain viability and proliferation of the developing cells

Front 5

What are the three families of an Ig gene segment

Back 5

Variable (V), Joining (J), Diversity (D)(Heavy chain only)

Front 6

What is somatic recombination

Back 6

The process by which V, D, and J segments are brought together to form functional BCR/Ig.

Front 7

What makes up the recombination machinery

Back 7

Recombination signal sequences (RSS) in the DNA; Recombination activating genes (RAG-1, RAG-2); DNA repair enzymes

Front 8

How is additional junctional diversity generated in the variable regions

Back 8

By the imprecise nature of DNA cleavage and repair at the junctions between recombined gene segments

Front 9

What is allelic exclusion

Back 9

Expression of a functional heavy chain at the cell surface inhibits further heavy chain recombination

Front 10

What is a surrogate light chain

Back 10

Because the heavy chain cannot be expressed on the cell surface without a light chain, a surrogate light chain is produced to allow heavy chain expression before recombination has occurred at the light chain loci.

Front 11

What is a pre-B cell receptor

Back 11

The complex formed by the newly recombined heavy chain and the surrogate light chain

Front 12

What are the developmental stages of a B cell

Back 12

1. Stem cell
2. Early pro-B cell
3. Late pro-B cell
4. Large pre-B cell (characterized by the pre-B cell receptor)
5. Small pre-B cell
6. Immature B cell
7. Mature B cell

Front 13

Developing B cells require interactions with what for their continued survival and proliferation

Back 13

Bone marrow stroma. Important stromal components include adhesion molecules and growth factors such as stem cell factor (SCF) and Interleukin-7

Front 14

What two processes contribute to the removal or inactivation of auto-reactive B cells

Back 14

Clonal deletion (B cells that respond to self antigens while still in the bone marrow)
B cell anergy (B cells that resond to soluble self antigens are signaled to enter a harmless, non-responsive state)

Front 15

Where do naive immature B cells migrate to after leaving the bone marrow

Back 15

Secondary lymphoid tissues

Front 16

How do B cells gain access to secondary lymphoid tissues

Back 16

Via high endothelial venules

Front 17

Where do B cells concentrate in the lymph nodes

Back 17

In the lymph node cortex, called primary lymphoid follicles

Front 18

What cells do B cells interact with in the B cell area

Back 18

Follicular dendritic cells, which provide survival signals to the B cells

Front 19

At what point is B cell development arrested

Back 19

An immature, naive state until the B cell encounters the specific antigen to which the cell surface BCR/Ig can bind. Antigen recognition stimulates proliferation and terminal differentiation

Front 20

What are germinal centers

Back 20

Foci of proliferating B cells in the lymph node cortex

Front 21

What is a secondary lymphoid follicle

Back 21

A lymphoid follicle containing a germinal center

Front 22

What are plasma cells

Back 22

Mature, terminally differentiated B cells that are committed to producing large quantities of Ig

Front 23

Where do plasma cells primarily reside

Back 23

In the medullary cords of the lymph modes and in the bone marrow

Front 24

What does alternative splicing of heavy chain mRNA result in

Back 24

Production of heavy chain proteins that lack the transmembrane region

Front 25

What is affinity maturation

Back 25

Switching to production of soluble Ig accompanied by refinement of the Ig specificity to produce Ig molecules of higher affinity

Front 26

What is somatic hypermutation

Back 26

A process where affinity maturation is achieved by rapid and random introduction of point mutations to the Ig variable regions

Front 27

What enzyme is required for somatic hypermutation and affinity maturation

Back 27

Activation-induced cytidine deaminase (AID)

Front 28

What is isotype switching (class switching)

Back 28

A process where Ig molecules with different functions are produced by pairing the variable antigen-binding region of the Ig molecule with different heavy chain constant regions that possess different properties

Front 29

What are the different heavy chain constant regions encoded by

Back 29

A cluster of C gene segments

Front 30

What are some diseases associated with B cell abnormalities

Back 30

1. B cell neoplasias (Acute lymphoblastic leukemia, Pre-B cell leukemia, Burkitt's lymphoma, Hodgkin's lymphoma, Multiple myeloma[Bence-Jones proteins])
2. B-cell mediated autoimmunity
3. B cell immunodeficiencies