Immunology (BIOL 318) Lecture 13

T cell maturation </3

3 main subsets of peripheral B cells

• Follicular

• Marginal zone

• B-1 cells

Steps to make lymphocytes

• Commitment (to B or T cell lineage)

• Proliferation

• Rearrangment/recombination

• Selection

• Differentiation

Pro-T cells can commit to either ____ or ____ lineages

αβ; γδ

EBF, E2A, and PAX5

• Transcription factors that induce the expression of genes required for B cell development

• Common lymphoid progenitor → pro-B cell

GATA3

• Transcription factor that induces T cell commitment

• ILC precurser → pro-T cell

DLL4 (delta-lke ligand 4)

• Ligand expressed by thymic epithelial cells

• Binds to NOTCH1 on ILC precursor cell surface

• Triggers signal cascade to upreglate GATA3

NOTCH1

• Receptor on ILC precursor cells that leads so signalling cascade resulting in commitment to the T cell lineage (both αβ and γδ)

• After commitmen to T cell lineage, it remains important in αβ lineage development

Gene expression upregulated by GATA3

• T cell maturation

• Genes to encode components of pre–T-cell receptor (pre-TCR) and the RAG1 and RAG2 proteins (required for V(D)J recombination)

IL-7

• Induces proliferation of progenitor cells in the lineage → more pre- cells

• Produced by strongly cells in the bone marrow or thymus

RAG1 and RAG2

Enzymes that form a complex and cut the recombination signal sequences between the V(D)J sequences

Signal ends

Coding ends

Artemis

TdT

DNA ligase IV

Purpose of rearrangment of antigen receptor genes in Ba and T cells

• To generate a diverse adaptive immune repertoire

• Recombination results in a large number of variable region–

  encoding exons

Recombination signal sequences (RSS)

• Conserved sequences of noncoding DNA

• These sequences FLANK V(D)J (V(D)J sequences are not RSS themselves)

• RAG1 and RAG2 bind here

12/23 bp rule

CCR7

CCR9

CD44

DN1 expresses…

DN2 expresses…

DN3 expresses…

DN4 expresses…

How are the immunoglobulin (Ig) heavy-chain locus and TCR β gene locus transcriptionally activated?

• Lineage-determining transcription factors bind to the loci

• Heterochromatin → euchromatin DNA is now open to proteins that will mediate Ig gene rearrangement and expression