B cell and B cell-mediated

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B cell and B cell-mediated humoral immune
response Department of Immunology Fudan
University Wei Xu, Ph.D 021-54237749
wx2362_at_hotmail.com
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Adaptive immune response to pathogens
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Overview of the humoral immune response against
bacterial
B cells
plasma cells
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B lymphocyte 515 of peripheral
lymphocytes 25 lymph node and 45
splenic lymphocytes secret antibodies
(Ab) act as antigen-presenting cell (APC)
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B cells and humoral immune response

• 1. Surface molecules of B cell
• B cell subsets
• B cell development
• Function and significance

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1. Surface molecules of B cell
Surface receptor 1) B cell antigen
receotor (BCR) 2) BCR coreceptor
3) Cytokine receptor(CKR)
Surface functional molecules
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Surface receptor 1) B cell antigen
receotor (BCR)
BCR/mIgM
Membrane Ig (mIg) Mature B cell mIgM
mIgD BCR-Iga/Igß complex
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BCR-Iga/Igb complex
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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 200427931973
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Coreceptor of BCR
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BCR-Iga/Igb coreceptor complex
B cell epitope
B cell activation
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TCR-CD3
BCR-Iga/b
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3.Complement receptor, CR
CR2(CD21)EB virus receptor
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4.Cytokine receptor, CKR
IL-1R?IL-2R?IL-4R?IL-5R?IL-6R?
IL-7R, IFN-?R regulate the activation,
differentiation and function of B cells
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1. Surface molecules of B cell
Surface receptor 1) B cell antigen
receotor (BCR) 2) BCR coreceptor
3) Cytokine receptor(CKR)
Surface functional molecules
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Surface functional molecules

• MHC-I?II molecules
• co-stimulatory molecules

• CD40 most important csm for B cell activation

B cell
CD40
CD40L
T cell
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Two-signal activation model for T cells
activation
naive
co-stimulatory molecules
anergy
none
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Two-signal activation model for B cells
Signal 3
Signal 1 and signal 2 are not simultaneous But in
two steps, signal 2 from Th cells
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B cells and humoral immune response

• 1. Surface molecules of B cell
• B cell subsets
• B cell development
• Function and significance

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2?B cell subsets
B1 Marginal zone B MZ B Follicular B
FO B / B2
Innate immunity
Generally mentioned B cell
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B1 cells
in the peritoneal and pleural cavities and the
gut lamina propria. unique phenotype CD5,
CD19 Progenitors fetal liver generation and
maintenanceSpleen 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).
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Sjogren's Syndrome
Cells are stained with anti-surface
molecule-monoclonal Abs (fluorescent FITC/green
PE/red )
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
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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
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spleen
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GC
B
T
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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
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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 ?????
gastric lymphoma Campylobacter jejuni
?????? gastric lymphoma, small intestinal
disease Borrelia burgdorferi ?????
cutaneous lymphoma Chlamydia psittaci
?????? ocular lymphoma hepatitis C virus
HCV spleen lymphoma
Blood. 20061073034-3044
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Histopathologic illustration of MALT/MZ lymphoma
H pylorigastric MALT lymphoma
CD20 centrocyte-like MZ B
C jejuni
typical villous lymphocyte patient with
HCV-associated splenic lymphoma
H pylori (arrow)
C jejuniassociated IPSID
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Systemic lupus erythematosus
MZ B cell and SLE
B-lymphocytes, innate immunity, and
autoimmunity Muriel Viau, Moncef Zouali
Clinical Immunology 114 (2005) 17 26
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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 cells
BAFF
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FO B
Secret Ag-specific Abs Mediate humoral
immunity Act as APC Present pep/MHC-?
CD4Th Especially Soluble Ag
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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
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three major naive peripheral B-cell populations
B cell
High-affinity IgG
Immunol Rev 2004 197206
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B cells and humoral immune response

• 1. Surface molecules of B cell
• B cell subsets
• B cell development
• Function and significance

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Lymphoid lineage
Myeloid lineage
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• 3. Development of B cells
• Bone MarrowAg-independent
• Peripheral (LN/spleen)Ag-dependent

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development of B cells
Ag-independent
MZ B
FO B
Newly formed B
IgM IgD
FB precursor
Ag-dependent
Nat Rev Immunol 2005 5230
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Bone Marrow No antigen Peripheral lymphoid
organ Ag-stimulation
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1.pro B Ig H chainD-J
V-D-J rearrangement,Iga/Igß surrogate
Lchain 2 pre B L chain V-J
rearrangement CD19? CD20?MHC-II
3.immature B mIgM, negative
selection 4.mature B
mIgMmIgD,leave
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Surrogate light chain, SLC
SLC Vpre-B/l5
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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)
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B cells and humoral immune response

• 1. Surface molecules of B cell
• B cell subsets
• B cell development
• Function and significance

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Function of Antibodies
1. Neutralization
toxin pathogen
bind to them and block their
functional domain

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Neutralization of viruses
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Function of Antibodies
2. activate complement pathway, lyze pathogens
IgG /M -Ag
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3. Opsonization- enhance MF Phagocytosis
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4. Ab-dependent Cell-mediated cytotoxicity, ADCC
enhance NK killing
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5. Secreted IgA at the mucosal surface
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6. Pathological effects of IgE
Food Allergy
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