Principles of ImmunologyB Cell Development

3/16/06

“Hard work has a future payoff but laziness pays off now.”

Anonymous

Word/Terms List

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 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