INSTITUTE FOR IMMUNOBIOLOGY

B cell and B cell-mediated

humoral immune response

Department of ImmunologyFudan University

Wei Xu, Ph.D021-54237749

wx2362@hotmail.com

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