Lymphocyte Development and Antigen Receptor Gene Rearrangement Cont.

Question 1

What does negative selection of immature lymphocytes play an important role in maintaining?

Answer 1

Important mechanism for maintaining THE CENTRAL TOLERANCE to many self Ags.

Question 2

When does negative selection occur?

Answer 2

Shortly after Ag receptors are first expressed on developing B and T cells.

Question 3

What does negative selection do to harmful T and B cells?

Answer 3

• Harmful T Cells -> ELIMINATES harmful T cells whose Ag receptors bind strongly to self Ags present in the thymus.
• Harmful B Cells -> ALTERS harmful B cells whose Ag receptors bind strongly to self Ags present in bone marrow.

Question 4

Developing harmful T cells with a high affinity for self Ags are eliminated by apoptosis. What is this phenomenon known as?

Answer 4

Clonal Deletion

Question 5

Developing harmful B cells with a high affinity for self Ags undergo the second attempt in Ig gene rearrangement. What is this process called?

Answer 5

Receptor Editing

Question 6

What happens if receptor editing fails in self-reactive B cells?

Answer 6

Self-reactive B cells die, which is also called CLONAL DELETION.

Question 7

What type of B cell lineage do most B cells that develop from feta liver-derived stem cells differentiate into?

Answer 7

B-1 Lineage

Question 8

What type of B cell lineage do most B lymphocytes that arise from bone marrow precursors after birth give rise to?

Answer 8

B-2 Lineage

Question 9

What contributes to the differentiation of B-2 cells into follicular B-2 cells and marginal zone B-2 cells?

Answer 9

affinity of the BCRs for self Ags

Question 10

What are follicular B-2 cells?

Answer 10

recirculating lymphocytes

Question 11

Where are marginal zone B-2 cells found?

Answer 11

Abundant in the spleen and can also be found in LNs.

Question 12

What do B-1 cells develop from?

Answer 12

feta liver-derived HSCs

Question 13

Why do B-1 cells express limited BCR diversity?

Answer 13

Because TdT is not expressed in the fetal liver.

Question 14

Where are a large number of B-1 cells found?

Answer 14

Found as a self-renewing population in the peritoneum and mucosal sites.

Question 15

What do B-1 cells spontaneously secrete?

Answer 15

Spontaneously secrete IgM Abs that often react with microbial polysaccharides and lipids as well as oxidized lipids.

these Abs are sometimes called natural antibodies because they are present in individuals without overt immunization

Question 16

What B cell type contributes most of the serum IgM during the early phases of infection?

Answer 16

B-1 B cells

Question 17

What do B-2 B cells develop from, and in what?

Answer 17

Develop from HSCs in the bone marrow.

Question 18

Following rearrangement of their BCR chain genes and removal of autoreactive cells via central tolerance, where do immature B-2 B cells relocate to?

Answer 18

Spleen

Question 19

What are the two different types of cells that immature B-2 B cells can differentiate into?

Answer 19

• MZ B Cells

- follicular B-2 Cells

Question 20

Where do marginal zone (MZ) B cells localize and what do they respond to?

Answer 20

• Localize -> to splenic marginal zone

- Respond to -> blood-borne Ags

Question 21

What do follicular B cells require?

Answer 21

constant replenishment from bone marrow

Question 22

What do follicular B-2 cells respond to?

Answer 22

Respond to protein Ags in a T cell-dependent manner, and progressively undergo immunoglobulin isotype switching and affinity maturation.

Question 23

True or False:

Only mature follicular B-2 cells upon T-cell-dependent activation develop into long-lived plasma cells or memory B cells.

Answer 23

True

Question 24

True or False:

Follicular B-2 cells are predominantly self-renewing.

Answer 24

False - MZ B cells are predominantly self-renewing.

Question 25

Is responses of MZ B cells independent of T cell help?

Answer 25

Yes

Question 26

Where specifically in the spleen are marginal zone B cells primarily located?

Answer 26

Vicinity of the marginal sinus in the spleen.

Question 27

What do the limited diversity BCRs of MZ B cells respond to?

Answer 27

Polysaccharide Ags and to generate natural Abs.

Question 28

Where can MZ B cells be found?

Answer 28

Spleen as well as in lymph nodes.

Question 29

What do marginal zone B cells respond very rapidly to?

Answer 29

blood-borne microbes

Question 30

What do marginal zone cells differentiate into after being exposed to blood-borne microbes?

Answer 30

short-lived IgM-secreting plasma cells

Question 31

True or False:

Although marginal zone B cells generally mediate T cell-independent humoral immune responses to circulating pathogens, marginal zone B cells also appear capable of mediating some T cell-dependent immune responses.

Answer 31

True

Question 32

True or False:

The rearrangement of TCR beta, gamma, or delta loci is initiated simultaneously.

Answer 32

True

Question 33

What percentage of developing T cells beome alpha-beta T cells?

Answer 33

90%

Question 34

What percentage of developing T cells become gamma-delta T cells?

Answer 34

10%

Question 35

If a cell first succeeds in productively rearranging its TCR gamma or TCR delta loci before it makes a productive TCR beta rearrangement, what happens?

Answer 35

It is selected into the gamma-delta T cell lineage.

Question 36

What causes limited diversity of expressed gamma-delta TCRs?

Answer 36

Because only a few of the available V, D, and J segments are used in mature gamma-delta T cells, for unknown reasons.