Transcript T Cell Development

Principles of Immunology
B Cell Development
3/16/06
“Hard work has a future payoff but laziness pays off
now.”
Anonymous
Word/Terms List
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Class switching
Clonal deletion
Naïve B cells
Stromal cells
TD antigens
TI antigens
B Cell Development
Maturation-Stem cells to mature,
naïve B cells
Activation-Ag binding; initiation of
cell changes
Differentiation-Cell division and
changes into effector B cells
(plasma cells) and memory B cells
Lymphopoiesis
 Occurs in yolk sac, fetal liver then bone
marrow throughout rest of life
 Mature, naïve B cells released into
circulation
 B cell production occurs throughout life;
does not wane as does T cell production
 About 5 million produced per day
 Only 10% of B cells mature
 Naïve B cells survive about one week
 Undergo negative selection
B Cell Maturation
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Hematopoietic stem cells(HSC)
Lymphoid stem cell (progenitor)
B cell progenitor (pro-B cell)
Pre-B cell
Immature B cell
 Mature, naïve B cell
B Cell Changes
 Pro B cells
 Rearrangement of Ig heavy chain genes
(D to J joining followed by V to DJ)
 Not all rearrangements result in
complete mu variable region sequences
 Expression of CD45R and CD19
 Further maturation is dependent on
direct interaction with BM stromal cells
 c-Kit on pro B is activated by SCF on
stromal cells
B Cell Changes
 Pre B cells
 Cell division occurs
 Rearrangement of Ig light chain genes (V to J
joining)
 Expression of IL7 receptor
 Expression of mu heavy chains in association
with Ig alpha-Ig beta heterodimer
 Pre B cell receptor uses surrogate light chains
 Shuts down further Ig gene rearrangement
B Cell Changes
 Immature B cells
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IgM expressed on surface
B cell receptor appears
Cells interact with self Ags
Negative selection (clonal deletion)
occurs
B Cell Changes
 Mature B cells
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Migrate out of bone marrow
Both IgM and IgD expressed on surface
Cell division occurs
Rearrangement of Ig light chain genes (V to J
joining)
Expression of IL7 receptor
Expression of mu heavy chains in association
with Ig alpha-Ig beta heterodimer
Pre B cell receptor uses surrogate light chains
Shuts down further Ig gene rearrangement
B Cell Activation
 Triggered by combining with Ag
 Two types of Ags that activate B cells
 Thymus dependent Ag
e.g. soluble proteins
 Thymus independent Ag
 Type 1, e.g. LPS
 Type 2, e.g. capsular polysaccharides
 The reaction to thymus independent
antigens is not as strong, memory cells
are not produced and class switching
does not occur
B Cell Activation
 Activation signals
 Two signals required
 In TI Ags both signals occur post antigen
binding without T helper cells
 In TD Ags, Ag binding provides one
signal and CD40/CD40L ligand on T
helper cell provides the second
B Cell Activation
 Signaling pathways
 Similar to T cell signaling
 Protein tyrosine kinase (Src)
 Phosphorylated tyrosines on ITAMS dock
the Syk kinase
 Ultimate effects are on gene expression
 Co receptor
 Three protein complex
 Provides signals that modify B cell
B Cell/T Cell Interaction
 B cells as Ag binding and Ag
presenting cells
 B cells are able to react to lower
concentrations of Ag
 Co-stimulation with CD40/CD40L
 Role of interleukins (IL2,4,5)
B Cell Subsets
 B1
 CD5 marker
 More responsive to CHO Ags
 Seen in peritoneum
 B2
 Most B cells (95%)
 Drive the Ag response in secondary
lymphoid organs
Humoral Response
 Effector cells and memory cells
 Naïve B cells vs. memory cells,
primary vs. secondary response