T Cell Development and B Cell Tolerance

Comprehensive fill-in-the-blank practice flashcards covering T cell development stages, thymus organization, positive and negative selection, lineage commitment models, MHC restriction experiments, and mechanisms of B cell tolerance.

T cell precursors originate in the bone marrow and migrate to the __________ to undergo development and maturation.

thymus

The complete process of T cell development within the thymus typically takes __________ weeks.

$$1\text{--}3$$

The thymus is fully formed at birth, reaches its maximum size at __________, and gradually atrophies with age.

puberty

During the early stages of T cell development, TCR gene rearrangements occur in an ordered progression in which the __________ chain rearranges prior to the $\alpha$ chain.

$$\beta$$

Double negative (DN) thymocytes are characterized by the lack of surface expression of both __________ and __________ coreceptors.

CD4; CD8

Commitment of precursor thymocytes to the T cell lineage by the late DN2 stage requires activation of key transcription factors, notably __________ and GATA-3.

Notch

Whether a developing thymocyte commits to the $\alpha/\beta$ or $\gamma/\delta$ lineage primarily depends on which __________ functionally rearranges first.

receptor

The pre-TCR assembled at the DN3 stage consists of a functionally rearranged TCR $\beta$ chain paired with the invariant __________ chain and CD3 signaling subunits.

$$\text{pre-T}\alpha$$

Signaling through the pre-TCR halts additional TCR $\beta$-chain locus rearrangements, a regulatory process termed __________.

allelic exclusion

Double positive (DP) thymocytes express both CD4 and CD8 coreceptors and represent approximately __________% of the total thymocyte population.

$$80$$

Positive selection of DP thymocytes occurs in the cortex and is mediated by __________, which present self-peptide:MHC complexes to select cells with intermediate affinity.

cortical thymic epithelial cells (cTECs)

Thymocytes whose TCRs fail to bind or bind with very low affinity to self-peptide:MHC complexes undergo death by neglect, accounting for __________% of DP thymocytes.

$$90\%\text{--}96\%$$

DP thymocytes possessing high affinity for self-peptide:MHC can undergo agonist selection to differentiate into __________.

regulatory T cells ($\text{T}_{\text{REG}}$) cells

Negative selection in the thymic cortex eliminates strongly self-reactive thymocytes and is primarily mediated by __________ and macrophages.

dendritic cells

Rolf Zinkernagel and Peter Doherty were awarded the 1996 Nobel Prize in Physiology or Medicine for discovering the principle of __________.

MHC restriction

In bone marrow chimera experiments, $(A \times B) F_1$ hematopoietic stem cells developing within a strain B thymus graft ($H2^b$) only kill LCMV-infected target cells of strain __________.

B

During lineage commitment of DP thymocytes, the transcription factor __________ promotes differentiation into CD4+ single-positive cells, whereas Runx3 specifies CD8+ single-positive cells.

Th-POK

According to the kinetic signaling model of lineage commitment, DP thymocytes initially downregulate __________ in response to positive selection.

CD8

In the kinetic signaling model, a disrupted TCR signal combined with __________ signaling instructs the thymocyte to commit to the CD8+ T cell lineage.

IL-7

Medullary thymic epithelial cells (mTECs) express the epigenetic regulator __________, which directs promiscuous expression of tissue-restricted antigens (TRAs).

AIRE (autoimmune regulator)

Patients with loss-of-function mutations in AIRE develop the autoimmune syndrome __________, resulting in widespread failure to delete tissue-reactive T cells.

autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED)

Newly exported T cells that have just exited the thymus into the periphery are called __________.

recent thymic emigrants (RTEs)

Exposure to IFN-$\gamma$ in professional APCs induces the immunoproteasome, replacing standard catalytic subunits with LMP2, LMP7, and __________.

LMP10

During MHC class I folding in the RER, the chaperone __________ stabilizes the free MHC class I $\alpha$ chain until $\beta_2$-microglobulin binds.

calnexin

In Goodnow et al.'s anti-HEL transgenic mouse model, expression of rearranged transgenic heavy and light chains suppressed endogenous BCR expression to only __________% of B cells.

$$1\%\text{--}6\%$$

Double-transgenic mice expressing both anti-HEL BCR and soluble HEL develop B cells with an anergic phenotype characterized by __________ and $\text{IgD}^{\text{high}}$.

$$\text{IgM}^{\text{low}}$$

Immature B cells exclusively express membrane IgM because the primary heavy-chain transcript is polyadenylated at Poly-A site __________.

$$2$$

Mature B cells co-express surface IgD and IgM through alternative cleavage and polyadenylation, preferentially cleaving at Poly-A site __________ to generate the $\delta_m$ transcript.

$$4$$