Transcript MZ B cells

INSTITUTE FOR IMMUNOBIOLOGY
B cell and B cell-mediated
humoral immune response
Department of Immunology
Fudan University
Wei Xu, Ph.D
021-54237749
[email protected]
Adaptive immune response to pathogens
Overview of the humoral immune response against bacterial
B cells
plasma cells
B lymphocyte
5％～15％ of peripheral lymphocytes
25% lymph node and 45% splenic lymphocytes
secret antibodies (Ab)
act as antigen-presenting cell (APC)
B cells and humoral immune response
1.
Surface molecules of B
cell
2. B cell subsets
3. B cell development
4. Function and significance
1. Surface molecules of B cell
Surface receptor
1) B cell antigen receotor (BCR)
2) BCR coreceptor
3) Cytokine receptor（CKR）
Surface functional molecules
Surface receptor
1) B cell antigen receotor (BCR)
BCR/mIgM
Membrane Ig (mIg)
Mature B cell： mIgM ＋ mIgD
BCR-Igα/Igβ complex
BCR-Iga/Igb complex
2. BCR coreceptor
Help and strengthen the BCR-Ag-signaling
CD19 B-specific surface marker
signal transduction
CD21 CR2，receptor for C3d-bound Ag
CD81 BCR－coreceptor ligation
induce reversible palmitoylation of CD81
to stabilize the CD19/CD21/CD81 complex
JBC 2004;279:31973
Coreceptor of BCR
BCR-Iga/Igb coreceptor complex
B cell epitope
B cell activation
TCR-CD3
BCR-Iga/b
3．Complement receptor, CR
CR2（CD21）：EB virus receptor
4．Cytokine receptor, CKR
IL-1R、IL-2R、IL-4R、IL-5R、IL-6R、
IL-7R, IFN-γR
regulate the activation, differentiation and
function of B cells
1. Surface molecules of B cell
Surface receptor
1) B cell antigen receotor (BCR)
2) BCR coreceptor
3) Cytokine receptor（CKR）
Surface functional molecules
Surface functional molecules
♣ MHC-I、II molecules
♣ co-stimulatory molecules
CD40: most important csm for B cell activation
B cell
CD40
CD40L
T cell
Two-signal activation model for T cells
activation
naive
co-stimulatory
molecules
none
anergy
Two-signal activation model for B cells
Signal 1 and signal 2 are not simultaneous
But in two steps, signal 2 from Th cells
Signal 3
B cells and humoral immune response
1.
Surface molecules of B
cell
2. B cell subsets
3. B cell development
4. Function and significance
2、B cell subsets
B1
Marginal zone B
MZ B
Follicular B
FO B
Innate immunity
/ B2
Generally mentioned B cell
B1 cells
in the peritoneal and pleural cavities and the gut lamina propria.
unique phenotype:
CD5, CD19
Progenitors： fetal liver
generation and maintenance：Spleen
produce ‘natural’ low-affinity IgM,
in response to self-antigens and bacterial antigens at mucosal site:
first line of defense
Associated with chronic lymphocytic leukemia (CLL).
Cells are stained with anti-surface moleculemonoclonal Abs (fluorescent: FITC/green; PE/red )
Sjogren's Syndrome
women with dry eyes and mouth,
chronic arthritis
Destroyed exocrine glands
T
B2
FACS analysis
B-1 cells are raised in autoimmune disorders and
accumulate in chronic lymphocytic leukemia (CLL).
CD5: T cell surface molecule
CD19: B specific marker
MZ B cells
innate immune functions
B-1 cells
（peritoneal cavity）
marginal zone (MZ) B cells （spleen）
frequent Ag encounter.
Secreting essentially germline-encoded, polyreactive natural Abs,
respond rapidly and vigorously to pathogens
express Toll-like receptors (TLR),
provide costimulation to GC B cells
important link between the innate and adaptive immunity
spleen
GC
B
T
Splenic B cells
Follicular B,
FO B
major B population
Marginal zone B, MZ B
Against blood-borne pathogens, mounting Abs.
Act as potent APC: lipid Ags
MZ B cell and B cell lymphoma
Infection-associated lymphomas derived from MZ B cells
MZ lymphomas
The list of microbial species :at least 5
Helicobacter pylori
幽门螺杆菌
Campylobacter jejuni
空肠弯曲杆菌 gastric lymphoma, small intestinal dis
Borrelia burgdorferi
博氏螺旋体
Chlamydia psittaci
鹦鹉热衣原体 ocular lymphoma
hepatitis C virus
HCV
gastric lymphoma
cutaneous lymphoma
spleen lymphoma
Blood. 2006;107:3034-3044
Histopathologic illustration of MALT/MZ lymphoma
H pylori–gastric
MALT lymphoma
C jejuni–associated IPSID
CD20 centrocyte-like
MZ B
H pylori (arrow)
C jejuni
typical villous lymphocyte
patient with HCV-associated
splenic lymphoma
Systemic lupus erythematosus
MZ B cell and SLE
B-lymphocytes, innate immunity, and autoimmunity
Muriel Viau, Moncef Zouali*
Clinical Immunology 114 (2005) 17– 26
The innate model of SLE pathogenesis:
central role of TLR-activated MZ-B cells and pDCs.
BAFF
mDC derived
BAFF promote
survival and
differentiation of
auto B cells
FO B
Secret Ag-specific Abs
Mediate humoral immunity
Act as APC
Present pep/MHC-Ⅱ
Especially Soluble Ag
CD4+Th
B1
B2/FO B
location
mucosal sites
spleen, LN
Ig-producing way
naturally
Ag-inductive
specificity
poly-reactive
highly specific
Ag
TI Ag
TD Ag
（polysaccharide）
Ig class
Ig M
IgG
affinity
low
high
three major naive peripheral B-cell populations
B cell
High-affinity IgG
Immunol Rev 2004; 197:206
B cells and humoral immune response
1.
Surface molecules of B
cell
2. B cell subsets
3. B cell development
4. Function and significance
Myeloid lineage
Lymphoid lineage
3. Development of B cells
Bone Marrow：Ag-independent
Peripheral (LN/spleen)：Ag-dependent
development of B cells
Ag-independent
MZ B
FO B
Newly formed B
FB precursor
Ag-dependent
IgM+ IgD+
Nat Rev Immunol 2005; 5:230:
Bone Marrow
No antigen
Peripheral lymphoid organ
Ag-stimulation
1．pro B
Ig H chain：D-J
V-D-J rearrangement，Igα/Igβ
surrogate Lchain
2
pre B
L chain V-J rearrangement
CD19、 CD20、MHC-II
3．immature B
mIgM, negative selection
4．mature B
mIgM＋mIgD，leave
Surrogate light chain, SLC
SLC: Vpre-B/l5
B lineage commitment
Myeloid cell
T
HSC
CD19
HSC (hematopoietic stem cell)
LMPP (lymphoid/myeloid progenitor)
ELP (earliest lymphocyte progenitor)
ETP (early T-lineage progenitor)
CLP (common lymphoid progenitor)
B cells and humoral immune response
1.
Surface molecules of B
cell
2. B cell subsets
3. B cell development
4. Function and significance
Function of Antibodies
1. Neutralization
toxin
pathogen
bind to them
and
block their
functional
domain
Neutralization of viruses
Function of Antibodies
2. activate complement
pathway, lyze pathogens
IgG /M -Ag
3. Opsonization- enhance MF Phagocytosis
4. Ab-dependent Cell-mediated cytotoxicity, ADCC
enhance NK killing
5. Secreted IgA at the mucosal surface
6. Pathological effects of IgE
Food Allergy