B Cell Response

B Cell Response

The basic process of humoral immune response

Antigenrecognition

B cellactivation

Plasmacell

MemoryB cell

Antibody

Two types of antigens

TD-Ag

TI-Ag

Initiate a B cell response in the presence of Th cell

Initiate a B cell response in the absence of Th cell

I. B cell response to TD-Ag

TD-Ag: composed of T and B cell epitopes

B cell epitope

Bind to BCR

T cell epitope (peptide)

MHC class II+ Bind to TCR

Antigen Recognition by BCR

Antigens recognized by BCR can be proteins, polysaccharides, nucleic acids, lipids, or small compounds.

BCR recognizes both linear and conformational epitopes.

They do not need not to be processed by APCs.

Signal Transduction following BCR Engagement

Signal Transduction following BCR Engagement

Signaling by B cell-co receptor

The B cell co-receptor is a complex of three proteins: CD19, CD21 and CD81. Complement-coated antigens cross-link BCR and the co-receptor. The long cytoplasmic tail of CD19 is then phosphorylated and serve as docking sites for a large number of signal transducers, thereby amplifying the BCR signal.

Dual-signal Model for B Cell Activation

anergy

Signal 1

Signal 2

Th

No Th

B

B

IFN- , IL-4, IL-5

Signal 1

activation

Signal 1 from BCR-antigen interactionSignal 2 from interaction between CD40 on B cells and CD40L on activated T cells

Antigen crosslinks mIg

generate signal ①

increased expression of MHC II and B7

Interaction of T-B Cells in B Cell Responses

activate Th cell

Th cell begins to express CD40L

CD40L-CD40 interactions provide signal ②

Th cell secreted cytokines

Germinal Center Reaction

The activated B proliferates extensively and forms a germinal center.

Important events in germinal center

Somatic hypermuatation

Follicular dendritic cells… not an APC! The follicular dendritic cells do not have MHC-II and B7 Expressing high levels of Fc receptor

Selection of mutated clones

Affinity maturation:The affinity of the antibodies increases progressively

Important events in germinal center

Antibody class switching

The antibodies produced in primary response are mainly IgM. But they switch to other classes (IgG, IgA and IgE) late in the response or in secondary response.

Cytokines and class switching

Generation of plasma and memory cells

Characteristics of plasma cells

Specialized Ab producing facility1000 molecules/secIncreased transcriptionShut-off of production of other proteins

Comparison of naïve and memory B cells

Kinetics of the Ab Response

Ag

D a y s A f t e r I m m u n i z a t i o n

A b

T i

t e

r

Lag Log DeclinePlateau

Lag: naive B cells undergo clonal selection, expansion, and differentiation.

Log: a logarithmic increase in serum antibody level

Plateau: reaches a peak, plateaus for a variable time

The secondary response

Activation of memory cells by antigen

results in a secondary antibody response

that can be distinguished from the primary

response in several ways.

Primary vs secondary response

The secondary response

has a shorter lag period

reaches a greater

magnitude and lasts longer Ab with a higher affinity for the Ag, and isotypes other than IgM

predominate

Primary vs secondary response

II. B cell response to TI-Ag

Two types of TI-Ag: TI-1 antigen and TI-2 antigen

different mechanistic properties

B cells response are different

TI-1 antigenTypical TI-1 antigens are LPS （ bacterial cell wall component）Induce activation of many B cells, both specific and nonspecific.

No: class switching, affinity maturation and memory Low affinity IgM

TI-2 antigen

Polysaccharides from bacterial cell walls

Polymeric protein structures such as bacterial flagella

What to remember

Primary vs secondary responsesT cell help for B cell responseCritical events in GC