institute for immunobiology b cell and b cell-mediated humoral immune response department of...
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INSTITUTE FOR IMMUNOBIOLOGY
B cell and B cell-mediated
humoral immune response
Department of ImmunologyFudan University
Wei Xu, Ph.D021-54237749
Adaptive immune response to pathogens
Overview of the humoral immune response against bacterial
B cells plasma cells
B lymphocyteB 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 cell2. B cell subsets3. B cell development4. Function and significance
Surface receptor
1) B cell antigen receotor (BCR)
2) BCR coreceptor
3) Cytokine receptor （ CKR ）
1. Surface molecules of B cell
Surface functional molecules
Membrane Ig (mIg)
Mature B cell ： mIgM ＋ mIgD
BCR-Igα/Igβ complex
BCR/mIgM
Surface receptor
1) B cell antigen receotor (BCR)
BCR-Ig/Ig complex
2. BCR coreceptor
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
Help and strengthen the BCR-Ag-signaling
JBC 2004;279:31973
Coreceptor of BCR
B cell activation
B cell epitope
BCR-Ig/Ig coreceptor complex
TCR-CD3 BCR-Ig/
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
Surface receptor
1) B cell antigen receotor (BCR)
2) BCR coreceptor
3) Cytokine receptor （ CKR ）
1. Surface molecules of B cell
Surface functional molecules
♣ MHC-I 、 II molecules
♣ co-stimulatory molecules
Surface functional molecules
CD40: most important csm for B cell activation
B cell
T cell
CD40
CD40L
Two-signal activation model for T cells
naive
activation
co-stimulatory molecules
anergynone
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 / B2
Innate immunity
Generally mentioned B cell
in the peritoneal and pleural cavities and the gut lamina propria.
unique phenotype:CD5, CD19
Progenitors ： fetal livergeneration and maintenance ： Spleen
produce ‘natural’ low-affinity IgM, in response to self-antigens and bacterial antigens at mucosal site:
first line of defense
B1 cells
Associated with chronic lymphocytic leukemia (CLL).
B-1 cells are raised in autoimmune disorders and accumulate in chronic lymphocytic leukemia (CLL).
CD5: T cell surface molecule
CD19: B specific marker
women with dry eyes and mouth, chronic arthritis
Destroyed exocrine glands
Cells are stained with anti-surface molecule-monoclonal Abs (fluorescent: FITC/green; PE/red )
B2
T
Sjogren's Syndrome
FACS analysis
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 cellsimportant link between the innate and adaptive immunity
MZ B cells
innate immune functions
spleen
B
T
GC
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
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 gastric lymphoma
Campylobacter jejuni 空肠弯曲杆菌 gastric lymphoma, small intestinal disease
Borrelia burgdorferi 博氏螺旋体 cutaneous lymphoma
Chlamydia psittaci 鹦鹉热衣原体 ocular lymphoma
hepatitis C virus HCV spleen lymphoma
Blood. 2006;107:3034-3044
MZ B cell and B cell lymphoma
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
B-lymphocytes, innate immunity, and autoimmunity
Muriel Viau, Moncef Zouali*
Clinical Immunology 114 (2005) 17– 26
MZ B cell and SLE
Systemic lupus erythematosus
The innate model of SLE pathogenesis: central role of TLR-activated MZ-B cells and pDCs.
mDC derived BAFF promote survival and differentiation of auto B cellsBAFF
Secret Ag-specific Abs
Mediate humoral immunity
Act as APC
Present pep/MHC- CD4Ⅱ +Th
Especially Soluble Ag
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
B1 B2/FO B
three major naive peripheral B-cell populations
B cell
Immunol Rev 2004; 197:206
High-affinity IgG
B cells and humoral immune response
1. Surface molecules of B
cell
2. B cell subsets
3. B cell development
4. Function and
significance
Lymphoid lineageMyeloid lineage
3. Development of B cells
Bone Marrow ： Ag-independent
Peripheral (LN/spleen) ： Ag-dependent
development of B cells
Newly formed B
FB precursor
Nat Rev Immunol 2005; 5:230:
Ag-independent
Ag-dependent
MZ B
FO B
IgM+ IgD+
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
SLC: Vpre-B/l5
Surrogate light chain, SLC
T
B lineage commitment
Myeloid cell
HSC (hematopoietic stem cell) LMPP (lymphoid/myeloid progenitor) ELP (earliest lymphocyte progenitor) ETP (early T-lineage progenitor)
CLP (common lymphoid progenitor)
HSC
CD19
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 M 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
