IMM2011 Lecture 7: Lesson #3- t and b cell development
23 Jun 2018
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LESSON #3:T development and central tolerance:
○ T and B cells develop in different locations
○ T cells originate from the bone marrow as precursor cells BUT
they develop in the THYMUS
○ Before entering the thymus they are not yet true T cells
○ B cells develop in the BONE MARROW
○ The thymus and bone marrow are called PRIMARY LYMPHOID
ORGANS because they are sites of T and B cell development
○ In contrast, lymph nodes and the spleen, which are spread
throughout the body and are where immune responses are
generated, are called SECONDARY LYMPHOID ORGANS
Key stages to b and t cell development:
1) Step 1 COMMITMENT:
- First stage of lymphocytes development
- both are from haematopoietic stem cell making a decision to
become either b or t cell.
- Small number of bone marrow precursors that migrate to primary
lymphoid to develop into billion of lymphocytes.
For T cells develop in the thymus
For B cells this occurs in the bone marrow
These starting cells undergo significant proliferation before entering the
next stage of development.
Step 2: PROLIFERATION: progenitor cell number expand for diversity
of antigen receptor expression.
expansion of progenitor cell numbers in preparation for antigen receptor
expression
● Cytokine IL-7 drives Progenitor lymphocytes to proliferate and
expand
● Cytokine is secreted by non T or B cell and binds to IL-7 receptor
on progenitor cell surface.
● These progenitor cells don't have antigen receptor yet
● IL-7 is a specific cytokine produced in the developing organ by
stromal cells that bind to the IL-7 receptor and induce the cell to
divide
● thymus, bone marrow and lymph nodes also have stromal cells -
cells that help the function of the organ.
●Within the thymus, the group of cells that include epithelial cells,
dendritic cells and macrophages are known as:stromal cells
Step 3: ANTIGEN RECEPTOR EXPRESSION: Rearrangement and
expression of antigen receptor genes (TCR and BCR)
Receptor expression part 1: Pre B/T cell antigen receptor
expression
Both TCR and BCR have two chains;
-TCR has α and β chains BCR/immunoglobulin has heavy and light
chains
○ When forming the receptor only one chain is made and tested -
called pre TCR OR BCR:
○ This ensure that the immune system saves energy before
making two faulty chains
○ Pre T cell: the beta chain is made first is paired with a pre-Tα
○ For the pre-BCR, the heavy chain is made first (and paired with
a surrogate light chain) and is known as a 'pre-B cell'
○ If the recombination does not make a functional chain then the
cell dies.
Allelic exclusion
- Ensure that each lymphocytes to have a single specificity
- Normally somatic cells have two copies of each combine- meaning
that two sites encode each of the VDJ gene segment for the
antigen receptor.
- Too prevent different specificity, the first functional chain BCR
heavy chain or TCR beta chain it will stop recombination at other
chromosome site.
Receptor expression part 2: Complete antigen receptor expression
● Proliferation for cell that have a functional b chain or heavy chain.
● Recombination occurs again to generate the second chain
● Light chain for BCR and alpha chain for TCR.
● Only cells with complete antigen receptor will survive.
Document Summary
T and b cells develop in different locations. T cells originate from the bone marrow as precursor cells but they develop in the thymus. Before entering the thymus they are not yet true t cells. B cells develop in the bone marrow. The thymus and bone marrow are called primary lymphoid. Organs because they are sites of t and b cell development. In contrast, lymph nodes and the spleen, which are spread throughout the body and are where immune responses are generated, are called secondary lymphoid organs. Key stages to b and t cell development: step 1 commitment : Both are from haematopoietic stem cell making a decision to become either b or t cell. Small number of bone marrow precursors that migrate to primary lymphoid to develop into billion of lymphocytes. For b cells this occurs in the bone marrow. These starting cells undergo significant proliferation before entering the next stage of development.
