Lymphocyte Development and Antigen Receptor Gene Rearrangement Cont. Flashcards
What does negative selection of immature lymphocytes play an important role in maintaining?
Important mechanism for maintaining THE CENTRAL TOLERANCE to many self Ags.
When does negative selection occur?
Shortly after Ag receptors are first expressed on developing B and T cells.
What does negative selection do to harmful T and B cells?
- 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.
Developing harmful T cells with a high affinity for self Ags are eliminated by apoptosis. What is this phenomenon known as?
Clonal Deletion
Developing harmful B cells with a high affinity for self Ags undergo the second attempt in Ig gene rearrangement. What is this process called?
Receptor Editing
What happens if receptor editing fails in self-reactive B cells?
Self-reactive B cells die, which is also called CLONAL DELETION.
What type of B cell lineage do most B cells that develop from feta liver-derived stem cells differentiate into?
B-1 Lineage
What type of B cell lineage do most B lymphocytes that arise from bone marrow precursors after birth give rise to?
B-2 Lineage
What contributes to the differentiation of B-2 cells into follicular B-2 cells and marginal zone B-2 cells?
affinity of the BCRs for self Ags
What are follicular B-2 cells?
recirculating lymphocytes
Where are marginal zone B-2 cells found?
Abundant in the spleen and can also be found in LNs.
What do B-1 cells develop from?
feta liver-derived HSCs
Why do B-1 cells express limited BCR diversity?
Because TdT is not expressed in the fetal liver.
Where are a large number of B-1 cells found?
Found as a self-renewing population in the peritoneum and mucosal sites.
What do B-1 cells spontaneously secrete?
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
What B cell type contributes most of the serum IgM during the early phases of infection?
B-1 B cells
What do B-2 B cells develop from, and in what?
Develop from HSCs in the bone marrow.
Following rearrangement of their BCR chain genes and removal of autoreactive cells via central tolerance, where do immature B-2 B cells relocate to?
Spleen
What are the two different types of cells that immature B-2 B cells can differentiate into?
- MZ B Cells
- follicular B-2 Cells
Where do marginal zone (MZ) B cells localize and what do they respond to?
- Localize -> to splenic marginal zone
- Respond to -> blood-borne Ags
What do follicular B cells require?
constant replenishment from bone marrow
What do follicular B-2 cells respond to?
Respond to protein Ags in a T cell-dependent manner, and progressively undergo immunoglobulin isotype switching and affinity maturation.
True or False:
Only mature follicular B-2 cells upon T-cell-dependent activation develop into long-lived plasma cells or memory B cells.
True
True or False:
Follicular B-2 cells are predominantly self-renewing.
False - MZ B cells are predominantly self-renewing.
Is responses of MZ B cells independent of T cell help?
Yes
Where specifically in the spleen are marginal zone B cells primarily located?
Vicinity of the marginal sinus in the spleen.
What do the limited diversity BCRs of MZ B cells respond to?
Polysaccharide Ags and to generate natural Abs.
Where can MZ B cells be found?
Spleen as well as in lymph nodes.
What do marginal zone B cells respond very rapidly to?
blood-borne microbes
What do marginal zone cells differentiate into after being exposed to blood-borne microbes?
short-lived IgM-secreting plasma cells
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.
True
True or False:
The rearrangement of TCR beta, gamma, or delta loci is initiated simultaneously.
True
What percentage of developing T cells beome alpha-beta T cells?
90%
What percentage of developing T cells become gamma-delta T cells?
10%
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?
It is selected into the gamma-delta T cell lineage.
What causes limited diversity of expressed gamma-delta TCRs?
Because only a few of the available V, D, and J segments are used in mature gamma-delta T cells, for unknown reasons.
