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Lecture 13 B Cells
B cells
58
Immunology
Undergraduate 4
04/04/2015

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Term
Where do pre-B cells colonize in the following species?

Fish
Avian
Mammals
Definition
Fish - pronephros
Avian - bursa of Fabricious
Mammals - bone marrow, Peyer's patches
Term
True or False

Unlike T cells, B-cells do not undergo negative selection
Definition
False

They undergo negative selection while in the bone marrow equivalent tissues
Term
When B-cells mature into plasma cells they secrete _____ as _____
Definition
BCRs as antibodies
Term
____ and ____ are collectively referred to as
Definition
immunoglobulins
Term
____ recognize free foreign antigens
Definition
B cells
Term
B cells secrete ____ while T cells secrete ____
Definition
immunoglobulins .... cytokines
Term
Which are able to recognize wider variety of antigens, B cells or T cells?
Definition
B cells
Term
What receptors to B cells express in the primary lymphoid organs?
Definition
IgM and IgD
Term
What do unstimulated B cells in secondary lymphoid organs secrete?
Definition
monomeric IgM
Term
What happens after B cells come in contact with T-dependent antigens in GCs?
Definition
-clonal expansion
-class switching from IgM to IgG/IgA/IgE
Term
What directs the heavy chain rearrangement required for class switching?
Definition
B cell CD40 ligation with Th cell CD154
Term
What cytokines are required in mice in order for production of IgG1 and IgE during class switching?
Definition
IL-4
Term
What cytokines are required in mice in order for production of IgG2a and IgG3 during class switching?
Definition
IFN-gamma
Term
What cytokines are required in mice in order for production of IgA during class switching?
Definition
TGF-beta
Term
Describe the chain composition of immunoglobulins
Definition
2 identical heavy chains
1 light chain
Term
What can the light chain be in mammals?
Definition
κ or λ
Term
What can the heavy chain be in mammals?
Definition
α, γ, δ, ε, or μ
Term
Describe the constant region of immunoglobulin heavy chains
Definition
made of several different domains, sometimes with a hinge region to provide flexibility (IgD, IgG, IgA)
Term
The trans-membrane domain of the BCR is _____ to transmit an activating signal and therefore is dependent on _____ for signaling
Definition
CD79 accessory molecules
Term
During B-cell activation, _____ on ____ act as docking sites for Src-tyrosine kinases ____ and ____
Definition
ITAMS on CD79
lyn and fyn
Term
Where do the co-stimulatory molecules required for B-cell activation come from? (2)
Definition
antigen-specific Th cells activated by DC during a primary immune response

OR

macrophage/B cell during secondary immune response
Term
What are the co-stimulatory signals for B cells to undergo clonal expansion & differentiation?
Definition
Th-cell CD154 - B cell CD40
Th-cell CD28 - B cell CD86
cytokines IL-4, 5, 6 and 13
Term
What co-stimulatory signal is required for B cell activation to T dependent/independent antigens?
Definition
CD21/CD19 complex
Term
What is required for a sustained B-cell response to occur?
Definition
TLR ligation with PAMPS e.g. TLR4
Term
What regulates antibody production in mammals?
Definition
Fc receptors

e.g. IgG levels reach a threshold, IgG ligates with CD32 and cross linking to BCR, inhibits further Ab production
Term
What are T-independent antigens?
Definition
antigens which can induce Ab production without the presence of Th cells
Term
The signal generated by T-independent antigens binding to B-cell TLRs & BCRs is not strong enough to cause _____ or _____
Definition
class switching or differentiation of memory B-cells
Term
What antibody will be acting it T-independent antigens are present?
Definition
only IgM (not strong enough signal to cause class switching)
Term
What do memory B-cells express to avoid death?
Definition
anti-apoptotic BCl-2
Term
Secondary immune responses will involve plasma cells which have already differentiated into ____, ____ or ____ rather than ____ or ____
Definition
IgG, IgE or IgA

IgM or IgD
Term
The long-term production of antibodies by B-cells depends on what?
Definition
PAMP stimulation of TLRs
Term
What antibodies are secreted from mucosal surfaces?
Definition
IgA and IgE
Term
What antibodies are secreted from lymph nodes, spleen and BM equivalent tissues?
Definition
IgM and IgG
Term
What antibodies are found in plasma?
Definition
primarily IgM and IgG

also IgA
Term
What antibodys are not found in fish or chickens?
Definition
IgG
IgE
Term
What is the major mammalian antibody during a secondary immune response
Definition
IgG
Term
True or False

IgG can activate the complement pathway
Definition
true
Term
What is the most ancient antibody isotype?
Definition
IgM
Term
IgM acts as what in its monomeric form?
Definition
as a BCR
Term
IgM is ____ in its antibody form
Definition
pentameric
Term
What is the major mammalian antibody during a primary immune response
Definition
IgM
Term
Which is more effective at complement activation, agglutination and opsonization, IgG or IgM?
Definition
IgM
Term
Describe the transport of IgA (3)
Definition
-transported through epithelial cells by poly-Ig Fc receptor
-receptor is degraded
-secretory component remains attached to IgA dimer to prevent degradation in gut
Term
What is the predominant antibody found in primate and pig milk?
Definition
IgA
Term
Which animal produce IgA?
Definition
birds and mammals
Term
What is the role of IgE?
Definition
acts as antigen-specific signaling receptor for sentinal cells (mast cells, eosinophils) to trigger degranulation during parasitic infections
Term
True or False

IgE has a long half life and is very stable
Definition
false
Term
IgD is found in which animals?
Definition
fish and mammals
Term
What is the hypothesized reason for expression both IgM and IgD (both are BCRs)
Definition
IgD is more flexible whereas IgM is not
Term
IgD has been found to attach to ____ and ____, eliciting strong inflammatory reactions
Definition
fish granulocytes and human basophils
Term
What is the evolutionary precursor of IgG and IgE?
Definition
IgY
Term
What immunoglobulin is unique to zebrafish? What is the equivalent in trout?
Definition
IgZ
IgT
Term
FCyRI, FCyRII and FCyRIII bind to which CD receptors?
Definition
RI - CD64
RII - CD32
RIII - CD16
Term
How is class switching from IgM to another isotype determined?
Definition
-looping out, cutting and re-splicing variable genes from the H chain and replacing them with isotype-specific H genes
Term
Are exons coding the secretory component & trans-membrane domain of IgM and IgD found at the 3' or 5' end?
Definition
3'
Term
True or False

Each isotype is coded for by one specific gene
Definition
False

May be coded for by multiple genes
Term
In bovines, IgG2 production is driven by ____ and is involved in ____
Definition
Th1 cytokines

CMIR
Term
In bovines, IgG1 production is driven by ____ and is involved in ____
Definition
Th2 cytokines

serum & milk
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