B Cell Response
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Transcript of B Cell Response
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B Cell Response
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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
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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
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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.
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Signal Transduction following BCR Engagement
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Signal Transduction following BCR Engagement
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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.
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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
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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
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Germinal Center Reaction
The activated B proliferates extensively and forms a germinal center.
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Important events in germinal center
Somatic hypermuatation
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Follicular dendritic cells… not an APC! The follicular dendritic cells do not have MHC-II and B7 Expressing high levels of Fc receptor
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Selection of mutated clones
Affinity maturation:The affinity of the antibodies increases progressively
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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.
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Cytokines and class switching
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Generation of plasma and memory cells
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Characteristics of plasma cells
Specialized Ab producing facility1000 molecules/secIncreased transcriptionShut-off of production of other proteins
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Comparison of naïve and memory B cells
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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
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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.
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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
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Primary vs secondary response
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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
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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
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TI-2 antigen
Polysaccharides from bacterial cell walls
Polymeric protein structures such as bacterial flagella
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What to remember
Primary vs secondary responsesT cell help for B cell responseCritical events in GC