12: Lymphocyte Development

Where do B and T cells develop from

Hematopoietic stem cells in the bone marrow

Regions of a TCR

Variable region and constant region

Where do B and T cells develop from

Hematopoietic stem cells in the bone marrow

Regions of a TCR

Variable region and constant region

Proteins that make up the variable region

αβ or γδ

Proteins that TCRs associate with for signal transduction

CD3 and ζ chains (both have ITAMs)

Types of co-receptors on a T cell

CD4 and CD8

Gene segments in the TCR genome

• V: variable

• D: diversity

• J: joining

• Constant regions

Which TCR gene is not always present

D

How does the genome ensure that the αβ or γδ segments stay paired

The δ segment is encoded in the α segment, so only one can be expressed

What receptors are on a thymocyte when it gets to the thymus for maturation

None :)

Recombination for an αβ receptor

• β chain is recombined

• If useful, a “half” TCR is expressed with both CD4/8, CD3, and pre α chain

• α chain is recombined

• If useful, cell expresses whole TCR with both CD4/8 and CD3

  • if not, the α chain rearrange and tries again

Nude thymocytes

Double negative T cell; no CD4 or CD8

Double positive thymocyte

One that expressed both CD4 and CD8

Where are γδ T cells usually found

Mucosa

In what class of animals are γδ T cells the predominant type

Ruminants

What type of molecules/antigens do γδ T cells recognize

Non-proteins and peptides

What presenting molecule is needed for γδ T cells to recognize antigens

CD1

What process makes a double positive T cell a single positive T cell

Positive selection

Positive selection process

• If the ++T cell interacts with MHC I, the CD4 is dropped and it becomes a CD8 cell

• If the ++T cell interacts with MHC II, the CD8 is dropped and it becomes a CD4 cell

What happens if a T cell doesn’t interact with MHC during positive selection

It gets destroyed

Negative selection process

The newly single positive T cell is introduced to self proteins to be tested for autoreactivity

How is negative selection mediated by the thymus

Thymus cells express the AIRE gene, which lets them express any gene in the body in order to test T-cells with the full complement of self proteins

Other name for negative selection

Central tolerance

What percentage of T cells makes it out of the thymus as a naive T cell

2%

Main function of B cells

Makes antibodies!

BCR structure

Membrane bound antibody

Proteins that BCRs associate with for signal transduction

Igα and Igβ (have ITAMs that can be phosphorylated)

Gene segments in the BCR genome

• 2 light chain loci

• 1 heavy chain locus

Regions in the BCR loci

• V

• D

• J

• Constant

Which region is not in the light chain genes

D

Which region determines the receptor/antibody isotype

Constant region of the heavy chain

Default receptor isotype of a B cell that hasn’t been stimulated by specific cytokines

IgM and IgD

How is class switching of BCRs mediated

Cytokine stimulation triggers the expression of a different heavy chain constant region gene, and the old isotype gene is clipped out and no longer can be expressed

BCR development process

• VDJ rearrangement of heavy chain genes

• Proliferation of pre-B receptor if the heavy chain is functional

• VDJ rearrangement of light chain genes

• IgM expressed

• IgD expressed

How can two receptors have the same VJ/VDJ combination but different BCRs

Insertions and deletions

Somatic hypermutation

The process where an activated B cell proliferates and the BCR becomes more antigen specific via editing the variable region or isotype switching

Which maturation process do TCRs undergo and BCRs don’t

Positive selection

Cell that mediates negative selection of B cells

Stromal cells in lymphoid tissues

What happens if a B cell attaches to a protein a stromal cell is presenting

It can rearrange, but often it dies

When B cells in secondary lymphoid tissues are activated, what structure shows up

Germinal centers

After a B cell has undergone some somatic hypermutation and decided the BCRs are specific enough, what does it form

Plasma cell that goes back to the bone marrow and blood