Response in infants Polyclonal activation B Cell types B cell responses to antigens In xid mice...
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Transcript of Response in infants Polyclonal activation B Cell types B cell responses to antigens In xid mice...
Response in infants
Polyclonal activation
B Cell types
B cell responses to antigens
In xid mice (BTK-)
Antigen types
B Cell Antigen Receptor
TI-2TI-1
MatureB cells
in general
B1 cells,marginal
zone B cells
Yes No
Yes No
NoYes
Bacterial cell wall
components
Highly repetitive structures
Indep. Dep.
T cell-independent
FollicularB cells
No
Yes
Yes
Proteins, CHO, lipids
Dep.
T cell-dependent
TI-1 antigens
- many are bacterial cell wall products, such as LPS,peptidoglycan, lipoprotein, porin
- many are recognized by Toll-like receptors
- potent but non-specific inducer of B cell proliferation
TI-2 antigens
- present on encapsulated bacteria and some viruses
- repetitive epitopes with regular spacing
- epitopes expressed on a rigid molecular backbone
- induce B cell response by cross-linking B cell antigen receptors
TLR
CR2
Modulation of TI-2 responses - second signals for activation
IL-2, IFN-,IL-3, GMCSF, IL5
T cells,NK cells
IC
(cognate recognition?)
TI-1 antigen(same or diff.Microbe)
TACI
BLys, APRIL
(1) B1 cells:
- Localized to the peritoneal and plueral cavities
- Their repertoire is skewed toward reactivity with TI-2 antigens;
- the inability of xid mice to respond to TI-2 antigens could be
due to the lack of B1 cells in these mice
- TI-2 activation of B cells, but not TD or TI-1, in vitro
results in a partial induction of the B1 phenotype
(2) marginal zone (MZ) B cells
- Localized to the perimeter of splenic white pulps
- Unlike follicular B cells, MZ B cells are not circulating
- with high levels of cell surface complement receptor 2 (CD21)
B cells reponsive to TI-2 antigens
TI response to particulate antigen,
(PC) Phosphorylcholine+ S. pneumoniae
MZ B1 B1
Spleen Peritoneal cavity
Plasmablasts Plasmablasts
bacteria bacteria
Question:
How are PC+ MZ B cells activated?
Study: Balazs et al, 2002. Immunity 17: 341-352
MZ B moves to DC
But not to M or neutrophils
C56BL/6 T-deficient
MZ B and DC with bacteriaPre-immune
Fig. 1 PC-specific MZ B migrates to DC after immunization
Conclusion of Fig. 1 - MZ B cells in close contact withdendritic cells containing bacteria
Experiments further showed:(1) the major cell type that capture bacteria from the blood is CD11clo dendritic cell
(2) CD11clo dendritic cells move from the blood to the spleen rapidly after immunization, and “present” the bacteria to the antigen-specific MZ B cells
(3) soluble factors, Blys and/or APRIL, derived from the CD11clo dendritic cells support the survival of these antigen-specific B cells; and is important for the full differentiation of the MZ B cells to plasmablasts
Fig. 3
Blood DC (CD11clo)or neutrophils that have phagocytosedbacteria migrate to spleen
Fig. 5 - Binding of soluble ligand to TACI is responsible for plasmablast differentiation of PC+ MZ B cells (in vitro)
Fig. 6
Binding of ligand to TACI is responsible for plasmablast differentiation of PC+ MZ B cells (in vivo)
1st division
2nd division
CMFDA assay for cell division
Fig. 7
Binding of ligand to TACI is responsible for survival of PC+ MZ B cells
TACI ligands
Activation of MZ B cells
Plasmablasts
Survival & differentiation
PC+ MZ B cells
TACI
PC+ MZ B cells
CD11clo blood DCmigrate to spleen aftercapture of bacteria
Fig.2
In vitro primedBMDC and PEC Mpromote plasmablast differentiation from PC+MZ B cells
Bacteria-primedblood DCpromote plasmablast differentiation fromPC+ MZ B cells
Fig. 4