White blood cells in the body

1. Principles of Immunology
B Cell Development
3/16/06
“Hard work has a future payoff but laziness pays off
now.”
Anonymous

2. Word/Terms List
 Class switching
 Clonal deletion
 Naïve B cells
 Stromal cells
 TD antigens
 TI antigens

3. 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

4. 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

5. 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

8. 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

10. 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

12. B Cell Changes
 Immature B cells
 IgM expressed on surface
 B cell receptor appears
 Cells interact with self Ags
 Negative selection (clonal deletion)
occurs

13. 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

14. 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

15. 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

17. 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

19. 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)

21. 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

22. Humoral Response
 Effector cells and memory cells
 Naïve B cells vs. memory cells,
primary vs. secondary response