Lymphocyte Development and Structure - Immunology

Introduction

B-Cell Development

B-cells develop in the bone marrow
- develop a unique B-cell receptor
- are tested to ensure that the receptor is functional
- are further tested for self-reactivity to prevent autoimmunity
This development cycle is coordinated by the orderly progression through stages where
- supporting cells give feedback at every stage
- interaction strength of the B-cell receptor is monitored

Stages of B-Cell Development
Cell Type	Developmental Steps	Surface Receptor	Associations
Lymphoid stem cell	Commitment to B-cell lineage	None	Pleuripotent
Pro B-cell	Heavy chain VDJ recombination Additional diversity from TdT modification	Heavy chain only	Recombination mediated by RAG proteins Defect in RAG leads to Omenn syndrome with no mature B cells
Pre B-cell	Allelic exclusion to ensure only one heavy chain expressed Positive selection Proliferation	Pre B-cell receptor	Key step in monitoring activity of the recombined heavy chain
Immature B-cell	Light chain VJ recombination Negative selection	IgM receptor	Inactivation of recombination machinery Key step in tolerance
Mature B-cell	Exit into blood stream	IgM receptor IgD receptor	Circulates and awaits activation by antigen

T-Cell Development

T-cells migrate from the bone marrow to the thymus where they
- develop a unique T-cell receptor
- are tested to ensure that the receptor is functional
- are further tested for self-reactivity to prevent autoimmunity
This development cycle is coordinated by the orderly progression through stages where
- supporting cells give feedback at every stage
- receptors that bind too strongly lead to developing T-cell death
- the T-cell receptor undergoes selection in distinct compartments

Stages of T-Cell Development
Cell Type	Developmental Steps	Surface Proteins	Associations
T-cell precursor	Commitment to T-cell lineage Migration to thymus	None	Lack of thymic development in DiGeorge syndrome
Double negative	Rearrangement of the β T-cell receptor chain Proliferation	Pre T-cell receptor	Occurs in the thymic cortex
Double positive	Rearrangement of the α T-cell receptor chain Expression of both CD4 and CD8 Positive selection against both class I and class II MHC	CD4 CD8 T-cell receptor	Occurs in the thymic cortex Key step in determining type of T-cell that develops MHC II binding leads to CD4+ cells MHC I binding leds to CD8+ cells
Single positive	Migration to medulla of thymus Negative selection against self antigens	T-cell receptor Either CD4 or CD8	The transcription factor AIRE allows medullary cells to express proteins from all areas of body This ensure tolerance to vast majority of self antigens
Mature T-cell	Exit into blood stream Awaits peripheral activation	T-cell receptor Either CD4 or CD8	Circulates and awaits activation by antigen