Chapter 8

Question 1

B and T lymphocytes arise from what?

Answer 1

a common bone

marrow–derived precursor that becomes committed to the lymphocyte lineage

Question 2

B cell maturation
proceeds in the bone marrow, whereas early T cell
progenitors migrate where?

Answer 2

complete their maturation in the thymus. Early maturation is characterized by cell proliferation induced by cytokines,
mainly IL-7, leading to an expansion in the
numbers of lymphocytes that have just committed
to individual lineages

Question 3

Extracellular signals induce the activation of transcription factors that induce the expression of what?

Answer 3

lineage-specific genes and open up specific antigen
receptor gene loci at the level of chromatin
accessibility

Question 4

B and T cell development involves the somatic

rearrangement of what?

Answer 4

antigen receptor gene segments
and the initial expression of the Ig heavy chain µ
protein in B cell precursors and TCR β molecules
in T cell precursors

Question 5

The initial expression of preantigen receptors and the subsequent expression
of antigen receptors are essential for what?

Answer 5

the survival,
expansion, and maturation of developing lymphocytes and for selection processes that lead to a
diverse repertoire of useful antigen specificities

Question 6

The antigen receptors of B and T cells are encoded

by receptor genes made up of what?

Answer 6

a limited number of
gene segments that are spatially segregated in the
germline antigen receptor loci but are somatically
recombined in developing B and T cells

Question 7

Separate loci encode the Ig heavy chain, Ig κ light
chain, Ig λ light chain, TCR β chain, TCR α and δ
chains, and TCR γ chain. These loci contain what?

Answer 7

V, J,
and, in the Ig heavy chain and TCR β and δ loci
only, D gene segments. The J segments lie immediately upstream of exons encoding constant
domains, and V segments lie a large distance
upstream of the J segments

Question 8

When present, D segments lie between where?

Answer 8

V and J clusters

Question 9

Somatic
rearrangement of both Ig and TCR loci involves
the joining of what?

Answer 9

D and J segments in the loci that
contain D segments, followed by the joining of the
V segment to the recombined DJ segments in these
loci or direct V-to-J joining in the other loci.

Question 10

This process of somatic gene recombination is

mediated by what?

Answer 10

a recombinase enzyme complex that includes the lymphocyte-specific components
Rag-1 and Rag-2.

Question 11

The diversity of the antibody and TCR repertoires

is generated by what?

Answer 11

the combinatorial associations of
multiple germline V, D, and J genes and junctional
diversity generated by the addition or removal of
random nucleotides at the sites of recombination.
These mechanisms generate the most diversity at
the junctions of the segments that form the third
hypervariable regions of both antibody and TCR
polypeptides.

Question 12

B cell maturation occurs in stages characterized by

different patterns of what?

Answer 12

Ig gene rearrangement and
expression. In the earliest B cell precursors, called
pro-B cells, Ig genes are initially in the germline
configuration, and D to J rearrangement occurs at
the Ig heavy chain locus.

Question 13

At the pro-B to pre-B cell transition, V-D-J recombination is completed at the Ig H chain locus. A
primary RNA transcript containing what?

Answer 13

the VDJ exon
and Ig C gene exons is produced, and the VDJ
exon is spliced to the µ C region exons of the
heavy chain RNA to generate a mature mRNA that
is translated into the µ heavy chain protein. The
pre-BCR is formed by pairing of the µ chain with
surrogate light chains and by association with the
signaling molecules Igα and Igβ. This receptor
delivers survival and proliferation signals and also
signals to inhibit rearrangement on the other
heavy chain allele (allelic exclusion

Question 14

As cells differentiate into immature B cells, V-J

recombination occurs initially where?

Answer 14

at the Ig κ locus,
and light chain proteins are expressed. Heavy and
light chains are then assembled into intact IgM
molecules and expressed on the cell surface.
Immature B cells leave the bone marrow to populate peripheral lymphoid tissues, where they complete their maturation

Question 15

At the mature B cell stage,
synthesis of µ and δ heavy chains occurs in parallel
mediated by what?

Answer 15

alternative splicing of primary heavy
chain RNA transcripts, and membrane IgM and
IgD are expressed

Question 16

During B lymphocyte maturation, immature B cells
that express high-affinity antigen receptors specific
for self antigens present in the bone marrow are
induced to do what?

Answer 16

edit their receptor genes or these cells
are eliminated. Receptor editing can involve further
rearrangement at the Ig κ locus and eventually also
involve Ig λ light chain gene rearrangement. B cells
that express λ light chains are frequently cells that
have undergone receptor editing

Question 17

T cell maturation in the thymus also progresses in

stages distinguished by the pattern of what?

Answer 17

expression
of antigen receptor genes, CD4 and CD8 coreceptor molecules, and location in the thymus. The
earliest T lineage immigrants to the thymus do not
express TCRs or CD4 or CD8 molecules

Question 18

. The developing T cells within the thymus, called thymocytes, initially do what?

Answer 18

populate the outer cortex, where
they undergo proliferation, rearrangement of TCR
genes, and surface expression of CD3, TCR, CD4, and CD8 molecules. As the cells mature, they
migrate from the cortex to the medulla

Question 19

The least mature thymocytes, called pro-T cells,

are what?

Answer 19

CD4−
CD8−
(double-negative), and the TCR
genes are initially in the germline configuration at
this stage. Rearrangement of the TCR β, δ, and γ
chain genes occurs at this stage.

Question 20

Selection processes drive maturation of what?

Answer 20

TCRexpressing, double-positive thymocytes and shape
the T cell repertoire toward self MHC restriction
and self-tolerance

Question 21

Positive selection of CD4+
CD8+
TCR αβ thymocytes requires what?

Answer 21

s low-avidity recognition of peptideMHC complexes on thymic epithelial cells, leading
to a rescue of the cells from programmed death

Question 22

As TCR αβ thymocytes mature, they move into where?

Answer 22

the medulla and become either CD4+
CD8−
or
CD8+
CD4−
. Lineage commitment accompanies
positive selection. It results in the matching of
TCRs that recognize MHC class I with CD8 expression and the silencing of CD4; TCRs that recognize
MHC class II molecules are matched with CD4
expression and the loss of CD8 expression

Question 23

Negative selection of CD4+
CD8+
TCR αβ doublepositive thymocytes occurs when?

Answer 23

these cells recognize, with high avidity, antigens that are present
in the thymus. This process is responsible for tolerance to many self-antigens. Medullary thymocytes
continue to be negatively selected, and cells that
are not clonally deleted acquire the ability to differentiate into either naive CD4+
or CD8+
T cells
and finally emigrate to peripheral lymphoid
tissues.