Overview B cell development T cell development 2/1/2005 BIOS - - PDF document

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Overview B cell development T cell development 2/1/2005 BIOS - - PDF document

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Topics Overview B cell development T cell development 2/1/2005 BIOS 486A / 586A 1 Lymphocyte development overview Ag receptors in B and T cells are immensely variable Diversity is generated during development by gene

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Topics

  • Overview
  • B cell development
  • T cell development

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Lymphocyte development overview

  • Ag receptors in B and T cells are

immensely variable

  • Diversity is generated during

development by gene rearrangement

  • Lymphopoiesis occurs mainly in Central

Lymphoid Tissues (Bone Marrow & Thymus)

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Lymphocyte development overview (Cont)

  • Receptor diversity is produced by gene

rearrangement and is random

  • Includes specificities that will bind to SELF
  • Lymphocytes go through a process of

selection

– Self-recognizing cells are removed from the system during development (Negative selection) – Sells that recognize self antigens weakly or that recognize self antigens in a particular way receive a survival signal (positive Selection)

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Lymphocyte development overview (Cont)

  • Negative Selection ensures Immunological

Tolerance

  • Positive Selection ensures MCH Restriction

(T-cells)

– Default fate = cell death

  • Most lymphocytes generated in the Bone

Marrow do not survive

  • In the fetus lymphocytes are generated in the

liver

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  • In the fetus and juvenile individuals:
  • large production of new lymphocytes that

populate the peripheral lymphoid tissues

  • In the mature individual:

– New T cell production slows down. T cells are maintained by division of mature T cells. – New B cells are constantly being produced

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Fig 6.1

4 stages of B cell development

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  • Development requires signals from to

microenvironment to start gene rearrangements

  • Stromal cells (Stroma = mattress)

– Specific adhesion contacts via interaction

  • f cell-adhesion molecules and their

ligands – Provide growth factors that stimulate lymphocyte differentiation and proliferation

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B cell early development in the Bone Marrow

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  • Development occurs in stages
  • is measured by successful

rearrangement of genes and expression

  • f receptor molecules
  • Development is accompanied by

expression of other cell surface and intracellular proteins

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  • Productive rearrangement leads to protein

expression

  • Non-productive rearrangement leas to apoptosis
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B cell development in Secondary lymphoid

  • rgans
  • Immature cells complete development in secondary

lymphoid organs

– Spleen, Lymph nodes, MALT

  • Small proportion complete maturation and survive to

recirculate between Lymphoid organs and the blood

  • Survival is a consequence of competition for a place

in the pool of long-lived recirculating B cells

  • Follicular dendritic cells, located in FOLLICLES

provide survival signals to all cells

  • B cells stay for one day in follicle

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B cell selection

Immature B cells (Bone Marrow) Mature B cells (Secondary Lymphoid tissues)

Binding to Ag presented by cells? (multivalent) NO YES Apoptosis Binding to soluble Ag? NO YES Anergy Enter the secondary lymphoid tissue? YES NO Short life

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T cell Development

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T cell origin

–Fetus : Bone Marrow & Liver –Infants, juveniles: Bone Marrow & Thymus – High production –Adults: Thymus atrophied – #s maintained by division of Mature T cells

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Thymic stroma

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Lymphid precursor B cell precursor B cell α:β γ:δ CD8

Cytotoxic T cells

CD4

T helper cells

T cell precursor Th 1 Th 2

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T cell development

Progenitor cells enter thymus Differentiate into

  • Dendritic cells
  • γ:δ
  • α:β

Double negative cells CD3- CD4- CD8- Double positive cells CD3+ CD4+ CD8+ β chain gene rearrangement α chain gene rearrangement Single positive cells CD3+ Either CD4+ or

  • r CD8+

Fig 7.3

Cortex Medulla

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MHC restriction

T cell

Antigen presenting cell MHCa MHCb MHCa

X X Y Fig 5.16 (a) (a) (a) (a) (a) (b)

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Co-stimulation / Adhesion Molecules

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Positive Selection of T cells

CD3+ CD4 +CD8+

Thymic APC Good interaction between TCR – MHC?

CD3+ CD4 +CD8+ CD3+ CD4 +CD8+ CD3+ CD4 +CD8+ CD3+ CD4 +CD8+

Rescue Ensures MHC restriction

YES

Death in 3 or 4 days

NO

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CD3+ CD4 +CD8+

Very strong interaction between TCR – MHC?

Negative Selection of T cells

Thymic APC

YES

Apoptosis

NO

CD3+ CD4 + CD3+ CD4 + CD3+ CD4 + CD3+ CD4 + CD3+ CD8+ CD3+ CD8+ CD3+ CD8+ CD3+ CD8+

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Fig 7.23 4th Ed

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Cell – Cell interactions in the Lymph Node

T cells enter lymph node T cells monitor APC If interaction, T cells proliferate and differentiate If no interaction, T cells leave Fig 8.2

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