Lecture # 7 B Cell Development

Question 1

What constitutes (or makes up) the pre-BCR?

Answer 1

heavy chains, Vbre, and lambda 5 (all three make up the surrogate light chain)

Question 2

What are the two checkpoint stages of B cell development?

Answer 2

The pre- B cell stage and the immature B cell stage

Question 3

Central lymphoid organs

Answer 3

Specialized tissue where lymphocyte development takes place (Bone marrow for B Cells)/ (Thymus for T Cells)

Question 4

Peripheral lymphoid organs

Answer 4

Specialized lymphoid organs where mature lymphocytes reside and circulate in the blood (spleen, lymph nodes, mucosal lymphoid tissue)

Question 5

Stages of B- Cell maturation

Answer 5

1) Stem cell 2) pro lymphocytes 3) pre lymphocytes 4) immature lymphocyte 5) Mature lymphocyte

Question 6

Which stage in B cell development is Antigen dependent?

Answer 6

The second checkpoint, immature B - cell. Tests against self antigens

Question 7

Why are stromal cells important in B cell development?

Answer 7

stromal cells have FLT3L, which B cell progenitors bind and cause them to differentiate to become B cells. Stromal cells also produce IL-7

Question 8

What two receptors are present on the surface of B-cell progenitors?

Answer 8

FLT3 and IL-7 receptors

Question 9

Why is IL-7 production important in B-Cell production?

Answer 9

IL-7 promotes the expression of E2A, E2A promotes the expression of EBF, EBF promotes the production of Pax-5 which are all important in B-cell development. Cause B cell to express CD19, Ig alpha

Question 10

What are events that mark the transition from the pro-B to pre-B cell?

Answer 10

upregulation of RAG and TdT. Goes from unrecombined (germline) DNA to Recombined H chain gene (VDJl u mRNA

Question 11

What surface marker is developing during the pro-B stage?

Answer 11

CD43+, CD10+, but most importantly CD19+

Question 12

BTK

Answer 12

Bruton’s Tyrosine Kinase. Deficiency in this gene cause lack of development of B cells. BTK is activated downstream of Pre-BCR to mediate proliferation and survival.

Question 13

X- Linked Agammaglobulinemia

Answer 13

Inherited inability to make antibodies; no tonsils (because the tonsils are just a big lymphoid organ that house b cells); deficiencies in b cells and their products

Question 14

CD19 vs CD3

Answer 14

CD19 (B-cell) CD3 (T Cell)

Question 15

When does D-J rearrangement of H chain occur?

Answer 15

Occurs in early pro-B stage.

Question 16

When does V-DJ rearrangement occur?

Answer 16

late pro-B on one allele (allelic exclusion) Successful rearrangement produces intact heavy u chain. Post VDJ pro B-cell becomes pre-B cell

Question 17

What happens to cells that do not produce an intact u H chain?

Answer 17

They are eliminated

Question 18

Why are checkpoints needed?

Answer 18

1) VDJ is random, imprecise and can result in unsuccessful rearrangement. 2) Tests for functional receptor

Question 19

The light Chain

Answer 19

The light chain is produced after the heavy chain is produced. The light chain and the heavy chain are produced on different chromosomes.

Question 20

Where does central tolerance occur?

Answer 20

The central lymphoid organs (In the bone marrow) . High avidity B cells either undergo receptor editing or apoptosis.

Question 21

Clonal deletion

Answer 21

Occurs when BCR bind strongly to self antigen-multivalent Ag cross-links BCR. Cell gets a very strong signal through IgM at the immature stage and dies.

Question 22

Clonal anergy

Answer 22

Occurs when BCR soluble self antigen-still cross-links BCR down regulates IgM and cell cannot be activated. Cell gets moderate signal and dies later.

Question 23

What is the receptor on B-cells? T-cells?

Answer 23

B cells CD19/ T-Cells CD3

Question 24

Clonal Ignorance

Answer 24

occurs when BCR binds soluble self antigen with low affinity, monovalent antigen—self reactive cell receives weak or no signal- cell still exists and in many cases does not encounter Ag.