Principles of ImmunologyB Cell Development
3/16/06
“Hard work has a future payoff but laziness pays off now.”
Anonymous
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 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
IgM expressed on surface B cell receptor appears Cells interact with self Ags Negative selection (clonal deletion)
occurs
B Cell Changes Mature B cells
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