Lecture 3 Flashcards
(126 cards)
1
Q
What antibodies do naive B-cells express?
A
IgM IgD
2
Q
What are the phases of the humoral immune response?
A
- Antigens bind to IgM and IgD (B-cell receptors) on a naïve B-cell, causing it to become activated.
- Under the influence of helper T-cells, and other stimuli, the activated B-cell (B-cell clone) proliferates and differentiates.
- Activated B-cell can:
- a. Become plasma cells that secrete IgM
- b. Undergo isotype switching and become a Ig-G expressing B-cell.
- c. Undergo affinity maturation, creating antibodies with increasing affinity for the antigen.
- d. Create memory B cells.
3
Q
Compare our primary and secondary immune response.
A
will differ in quality and quanitity
4
Q
What happens during our primary immune response?
A
- Antigens activate naïve B cells.
- Activated B-cell will then differentiate into plasma cells that release IgM>IgG.
5
Q
What happens during our secondary immune response?
A
Secondary immune response- the same antigen will stimulate the memory cells that we made in our primary immune response, leading to the production of IgG>IgM.
- More antibodies are made.
- Isotype switching occurs
- Affinity maturation (increasing affinity) occurs.
6
Q
A
Secondary responses has higher average affinity due to affinity maturation.
7
Q
[Q:] What is the predominant antibody isotype in our primary response and our secondary immune response?
A
Primary- IgM
Secondary- IgG and sometimes IgA/IgE.
8
Q
[Q:] What induces the primary response?
A
All immunogens.
9
Q
[Q:] What induces the secondary response?
A
Mainly protein antigens.
10
Q
Types of B cells
A
- Follicular B2 cells
- Marginal zone B cells
- B1 cells
11
Q
Follicular B2 Cells
Where are they located?
T-cell dependent/independent?
Bind:
Produces:
A
- Circulate in spleen and other lymphoid organs
- T-dependent
- Bind: protein antigens
- Becomes a long lived plasma cell that have undergone isotype switching (IgG, IgA and IgE) and have a high affinity.
12
Q
Marginal Zone B Cell
Where are they located?
T-cell dependent/independent?
Bind:
Produces:
A
- Circulate in spleen and other lymphoid organs
- T-independent
- Bind: multivalent antigen
- Becomes short-lived plasma cell that releases IgM
13
Q
B1 B Cell
Where are they located?
T-cell dependent/independent?
Bind:
Produces:
A
- Located mucosal sites, peritoneal cavity
- T-independent
- Respond to: multivalent antigens
- Becomes short-lived plasma cell that releases IgM
14
Q
_____ are widely distributed throughout the body and continually replaced from the bone marrow.
A
B2 B-cells
15
Q
Name that cell.
Diversity is high.
Memory- yes
Underwent isotype switching
A
B2B cell
16
Q
B1 B-cells
Arise from what?
Where are they located?
A
Arise from the fetal liver by the 8th week of gestation.
Respiratory and GI system.
17
Q
Name that cell:
Diversity is low
Memory- very little
Undergo limited isotype switching
A
B1 B-cells
18
Q
What cells bridge the innate and adaptive immune system?
A
B1 B cell
19
Q
In order to initiate a antibody response, the antigen must be transported where?
A
Where B-cells are located: LN or spleen
20
Q
B2 B cells are located in follicles in our LN. How do they get there?
A
B2 B cells (aka recirculating B cell) recirculate in our blood from one to another secondary lymphoid organ.
- Once in the secondary lymphoid organ, they go to the B-cells zones (also called follicles) using CXCL13, a chemokine secreted from follicular DCs, as a guide
21
Q
What is CXCL13?
A
A chemokine released from follicular DC that guide B2 B cells home (into the follicles of LN).
22
Q
How do antigens get delivered to the Follicular B2 B cell, located in the follicle of LN?
A
Antigens can be delivered in many forms and many routes.
- Afferent lymphatic vessels that drain into the subscapular sinus of the LN.
- Soluble antigens (smaller than 70kD) can interact directly with B-cells in the follicle.
- Large antigens are transported to the follicles by resident FDCs.
- Pathogens and Ag-Ab complexes are captured by subscapular sinus macrophages, and deliver the antigen to the follicle.
23
Q
Properties of FDCs
A
- They do not express class II MHC.
- Do not phagocytose exogenous antigens and express them on class I MHC.
24
Q
What do FDCs do then?
A
- Secrete CXCL13 to help B cells and follicular T-helper cells migrate to the follicles.
- Can have [immune Ag-Ab complexes] on their surface for long periods of time.
- They play an important role during the germinal center reaction, as they release the substrate that drives affinity maturation
25
What cells are located in the **marginal zone (MZ)** of the **spleen**?
1. **MZ macrophages**
2. **Marginal B cells**
26
What forms the framwork of the marginal zone?
Fibroblasts.
27
How can lymphocytes and DCs can enter the white pulp?
To enter white pulp:
Pass through the cells that line the marginal sinus, which forms the barrier between the marginal zone and white pulp.
28
Marginal zone B cells that are located in the spleen can send antigens into the follicular region for Follicular B2 cells. How?
1. An [**immune complex**] binds to the **C2 compliment receptor** on the MZ B cell.
* Immune complex contain and *antigen* and has *compliment fragments*
2. MZ B-cell will then take it to the follicular region.
3. In the follicle, *FDC cells* (which have a high level of CR) complete with MZ B cells for binding of the complex.
4. Immune complex is trasferred to the FDC.
5. MZ B cells then go back to the marginal zone.
29
How do MZ B Cells recognize antigens in the spleen?
MZ B cells recognize antigens in their **native conformation.** Thus, they are not processed by APCs.
* 1. If the antigen is a part of the immune complex, it can bind to the CR2 compliment receptor.
* 2. Plasmacytoid DCs take up pathogens in blood --\> spleen --\> take to MZ Bcells
* 3. MZ macrophages in the spleen take up **polysaccharide antigens** and displayed them or take to MZ B-cells
30
When an antigen binds to a B-cell, what can happen?
## Footnote
**(Antigen-dependent process)**
1. B-cell will express **proteins that promote survival and cell cycling**--\> increased survival and proliferation
2. Increased **B7 expression**--\> causes B cell to interact with helper T-cell
3. Increased expression of **cytokine receptors**--\> increases responsiveness to cytokines
4. Increased expression of **CCR7**--\>migrates from follicle--\> T-cell zone.
31
What are the components of the B-cell receptor complex?
1. **BCR**--\> transmembrane antibody
2. **Igalpha and Igbeta**
**Coreceptors**: CD19, CD21, CD32 (not a part of the complex, but associate with the complex)
32
What BCR do naive B cells have?
IgM or IgD
33
If is a naive B-cell class switches, what does it switch to?
**IgG, IgA, IgE**
34
**What are Igalpha and Igbeta?**
How are they linked together?
How are they associated with the BCR?
What is special about them?
**Invariant** signaling molecules that are a part of the BCR receptor complex.
- Linked together by **disulfide**
- **Noncovalently** associated with the BCR
- Have **ITAMs** on their cytoplasmic tail, which mediate the signaling molecule
35
Describe how the co-receptors associate with the BCR complex.
They associate with the BCR complex, especially when they are linked through [Ag-complement or Ag-Ab complex].
36
What is the purpose of co-receptors?
Depending on which co-receptors are used, the signaling of the complex can be enhanced or inhibited.
37
Coreceptor CD19
The dominant signaling component of B-cell
38
Co-receptor CD21
CD21 is the **compliment receptor 2 (CR2)**
39
Co-receptor CD21/19
Together, they **positively regulate** B cell activation and lower the Ag threshold for B-cell activation
40
CD32 (**FcyRIIIB**)
contains **ITIM** and negatively regulates BCR signaling
41
BCR signaling pathway to activate
**In B-cells, to initiate a signal you need to bring together (cross-link) two or more BCR (Igs).**
1. Antigen (signal 1) + costimulatory molecule (signal 2) bind to the cross-linked BCR receptor and activate.
2. BCR complex initiate signaling
3. **Src kinases (lyn, fyn, blk**), which are lipid anchors, phosphorylate ITAMs on Igalpha and Igbeta.
4. BCRs enter lipid rafts, where many adaptor and signaling molecules are located
5. **SH2 domains of Syk tyrosine kinases** bind onto the phosphorylated ITAMS and are activated by Src kinases.
6. Activated Syk phosphorylates *tyrosine* residues on **BLNK** (**B cell linker protein**).
7. It recruits other enzymes, which activate **Ras** and **Rac**, **PLCy2** and the **Btk** (bruton tyrosine kinase)
8. Activates the following signaling pathways
1. **Ras-MAP kinase pathway**
2. **PLC pathway**
3. **PKC-B pathwa**y
End result: activation of the B cell.
42
What is CD21 (CR2) and its role in B cell activation?
B-cells have a complex made up of [**CR2 (CD12) compliment receptor and CD19-CD81**]. CD19 contains ITAMS.
A pathogen opsonized by C3d can bind to both the CR2 receptor and BCR, greatly enhancing B-cell activation.
43
How does the microbe antigen get opsinized by C3d?
How does [microbe antigen+ C3d] become bound?
1. C3 --\> C3a and C3b.
2. C3b will bind to the microbe.
3. C3b --\> C3d.
4. CD2 (CD21) is a receptor on the B cell for C3d.
5. Thus, [C3d+Ag] binds to B-cells, with the BCR recognizing the antigen and the CR2 recognizing the C3d.
44
**CR2-CD19-CD81** is often called what?
**B-cell coreceptor complex**
45
What is the mechanism of CR2 signaling?
1. When C3d-CR2 binds, *CD19-CD81* moves close to the BCR associated kinases.
2. **CD19 cytoplasmic tail** becomes **tyrosine phosphorylated**.
3. Follows the recruitment of *Lyn* kinase, which amplifies BCR signaling.
46
PAMP recognition + TCR signaling can activate B-cells as well. How?
*TLRs* and their *PAMPs* can activate B cells by **activating NF-kB signaling cascade.**
Microbial antigen will bind to Ab, causing BCR signaling. At the same time, TLR can recognize PMP and undergo TRL signaling, activating the NF-kB signaling cascade.
47
Research on TLR signaling in B cells has generated enormous interest. Why?
Because of its potential use in vaccines.
When a Bcell is stimulated with a TRL ligand--\> B-cell proliferation and differentiation--\> plasma cells.
Thus, TLR signaling in B cells accounts for **adjuvant (booster) effect** in any immunizations.
48
Antigen stimulation induces the ____ phase of the humoral response.
EARLY.
Antigen activated B cells causes proliferation, differentiation and can also secrete IgM, inducing the early phase of the humeral immune response.
49
B cell activation by antigen (and other signals) initiates the proliferation and differentiation of the cells and prepares them to interact with helper T lymphocytes if the antigen is a \_\_\_\_\_\_\_\_.
**PROTEIN**
50
What are the functional consequences of B-cell activation by an antigen?
1. Activated B-cells can express protein that increase survival and proliferation.
2. Activated B-cells can present antigens and B7, causing them to interact with helper T-cells.
3. Activated B-cells can increase expression of cytokine receptors to increase the responsiveness to cytokines.
4. Activated B-cells can increase expression of CCR7, causing the migration from follicle--\> T-cell zone.
5. Activated B-cells can generate plasma cells and secrete antibodies (IgM)
51
Explain the mechanism of how B-cells present Ag to T-cell.
1. Activated B cells endocytose protein antigen that binds specifically to the B cell receptor, resulting in degradation of the antigen and display of peptides bound to class II MHC molecules.
2. The helper T-cell recognizes the MHC-peptide complex on the B-cell
3. Activated helper T-cells begin to express CD40L and secrete cytokines
4. Both bind to their receptors on the same B-cell and proliferation and differentiation.
* a. Short-lived plasma cells that produce IgM are generated
5. B cells then migrate to germinal centers and undergo germinal center reaction
* a. *Somatic mutation*
* *b. Affinity maturation*
* *c. Isotype switching*
* *d. Generation of memory B cells*
* *e. Long-lived plasma cells that make IgG, IgA, IgM, IgE.*
6. B cells that have been activated by T helper cells at the edge of a primary follicle migrate into the follicle and proliferate, forming the dark zone of the germinal center . Germinal center B cells that underwent [isotype switching and somatic mutation]à light zone, where B cells with the highest affinity Ig receptors are picked to survive and differentiate into plasma cells or memory cells, which leave the germinal center.
52
**Extrafollicular B-cell reaction**
Occurs where?
What are the T-cells involved?
Characteristics.
Occurs: **medullary cords of the LN, between the [T-cell zone and red pulp] of the spleen**
T cells involved: **extrafollicular helper T-cells**
* Limited class switching occurs
* Somatic mutation rate is low
* Antibody affinity is low
* *Terminally differentiated B cells: Short lived plasma cells with a life span of 3 days.*
53
**Follicular/Germinal center B-cell reaction**
Occurs where?
What are the T-cells involved?
Characteristics.
Terminally differentiated B cells:
Occurs: **Secondary follicles**
T-cells involved: **TFH cells in the germinal center**
* Extensive *class switching* occurs
* *Somatic mutation* rate is high.
* Antibody affinity is high
Terminally differentiated B cells: long-lived plasma cells, which migrate to the bone marrow or MALT and memory cells
54
generation of TFH cells requires what?
sequential activation of T cells by
1. **Dendritic cells**
2. **Activated B cells**
55
After TFH cells are formed, whatt happens?
--\>[germinal center]--\> activate B cells.
56
TFH cells secrete \_\_\_\_, which is required for GC development and generation of plasma cells.
They also secrete\_\_\_\_\_\_, which controls isotype Th1/Th2 switching.
**IL-21**
**IFN-y or IL-4**
57
B-cells cause previously activated T-cells to \_\_\_\_\_\_\_\_\_\_\_\_\_
become TFH cells **4-7 days after antigen exposure**
58
**TFH cells** are important in GC formation and function and the activation and differentiation of B cells in these reactions. why
they express:
1. **ICOS** (inducible costimulatory)
2. **PD-1** (programmed death-1)
3. **IL-21**
4. T**ranscription repressor (Bcl-6)**
59
The germinal center is located within the follicle of a LN and has 3 zones:
1. **Dark zone**- contains proliferating B cells
2. **Light zone**- contains follicular DC cells
3. **Mantle zone**- surrounds GC and contains tightly packed small B cells of the primary follicle, pushed aside by GCs
60
Activated B cells--\> \_\_\_\_\_\_\_--\>\_\_\_\_\_\_\_\_\_\_; forms a dark zone.
Here, what happens?
follicle--\> proliferate
These B-cells undergo somativ hypermutation.
61
From the dark zone, B cells --\> [\_\_\_\_\_ zone] --\> encounter [**follicular DCs with antigen] & [TFH cell**s].
what happens?
light zone
- isotype switching
- affinity maturation- B cells wil highest affinity survive and become *plasma cells and memory B*
62
what b cells survive and differentiate into
- Plasma cells
Memory B cells
B cells with the highest affinity Ig
63
fate of plasma cells made in light zone?
leave and live in **bone marrow** as long lived plasma cells
64
fate of memory B cells made in light zone?
enter recirculating **lympcyte pool**
65
Heavy-chain isotype switching is induced by a combination of \_\_\_\_\_\_\_, _______ and ______ released from ____ cells. It occurs in germinal centers and allows plasticity in the humeral immune response.
- CD40L signals
- AID (activation-induced deaminase) activation by CD40
- cytokines
**TFH**
66
Heavy chain isotype switching occurs in ________ and allows ____ in the humeral immune response.
germinal centers
plasticity
67
In isotype switching, what changes?
Constant regions of the heavy chains are changed to switch the class of the antibody
68
\_\_\_\_\_ induces IgG switching.
How?
IFN-y
1. Intracellular pathogens activate **Th1 cells --\> IFN-y**
2. causing **TFH cells--\> IFN-y.**
69
\_\_\_\_\_\_ induces IgE switching.
How?
IL4 via TH2
Helminths cause **TFH** cells to release IL-4, which makes Th2 type cytokines during the germinal reaction
Eliminates helminths, working with eosinophils and mastcells.
70
B-cells in different anatomic sites switch to different types of antibodies, controlled by the _____ at that site.
cytokines
71
For example, B cells in mucosal tissues will switch to \_\_\_\_\_, where they protext epithelial cells from interacting with micbrokes.
IgA
72
\_\_\_\_\_\_\_\_\_ stimulates a switch to IgA.
TGF-B (made by *Treg cells and macrophages*)
73
[Q:] What happens in immunodeficiencies related to the CD40-CD40L axis?
Isotype switching cannot occur.
74
The molecular mechanism of isotype switching, called \_\_\_\_\_\_\_\_\_\_, takes the previously formed VDJ exon encoding the V domain of an Ig μ heavy chain and moves it adjacent to a down- stream C region
Both isotype switching and affinity maturation are critically depend on \_\_\_\_\_\_\_\_\_\_\_\_\_
**class- switch recombination**
**AID**
75
How does CSR work?
- Mature B cells first produce IgM immunoglobulins
- Occurs in constant region of heavy chain and is regulated by cytokines.
- Every C gene is preceded by a switching (S) sequence that controls the rearrangement process. CSR is proceeded by the expression of germline transcripts. The germline transcripts open the S region and make it accessible to recombination.
- CSR takes place between two SWITCH REGIONS (S), which has repetitive sequences of palindrome‐rich sequnces. DNA in between is cut out.
76
CSR is a “SWITCH” of the immunoglobulin isotype from IgM/IgD to IgG, IgA or IgE, with ______ **Ag specificity** but with ______ **biological properties**
similar
different
77
What is affinity maturation?
The process where the affinity of antibodies made in response to a **protein antigen** increases with prolonged or repeated exposure.
78
Affinity maturation is seen only in responses what?
T–dependent protein antigens.
79
Because of affinity maturation, the ability of antibodies to bind to a microbe or microbial antigen increases if what?
the infection is persistant or recurrent
80
This increase in affinity is caused \_\_\_\_\_\_\_\_\_\_\_\_, and particularly in the antigen-binding _________ regions, of the genes encoding the antibodies produced.
by point mutations in the V regions
hypervariable
81
Affinity maturation occurs in the germinal centers of lymphoid follicles and is the result of what?
Somatic hypermutation of **Ig V genes** in dividing B cells, followed by the selection of high-affinity B cells by antigen.
82
Why are mutations in IgV genes called somatic hypermutations?
In proliferating B cells in the dark zone of the GV, Ig V undergo point mutations at a extremely high rate: 1 in 10^3 base pairs, which is 1000x higher than spontaneous mutation. VH and VL genes each have about 700 nucleotides, resulting in 1 mutation/cell division.
83
Ig V gene mutation occur in the progeny of individual B cells. Thus, any B cell clone can gain more mutations during the life in the germinal center. **IgG anitbodies** from one clone of a B-cell can have as much as ____ of its germline sequence mutated (10 aa substitutions.
5%
84
Which have more mutations: IgM or IgG
IgG
85
\_\_\_\_\_\_\_\_\_\_\_\_\_ wil result from somatic hypermutation?
affinity maturation
86
How do we select what B cells survive?
- Only B cells with *high affinity for antigens* on follicular DCs are selective to survive.
- B-cells can also present antigens to germinal TFH cells, which uses CD40 to help B-cells survive.
87
Where do B cells die?
B-cells also die in germinal center because somatic mutation creates many B cells that do not have high affinity.
88
B cells that have undergone somatic mutation go where?
Follicular DC rich light zone.
89
B-cells with high affinity receptors are best able to bind the antigen when it is present at low concentration. B cells survive because of several mechanisms:
1. Antigen recognition causes the B cells to express anti-apoptotic proteins of the **Bcl-2 fam**.
2. They will endocytose and **present the antigen to TFH cells** in the germinal center, which signal via CD40L to promote the survival of B cells.
3. Can **activate endogenous inhibitors of Fas** and be protected from death.
Some TFH express FasL, which recognize Fas on B cells and causes apoptosis.
90
B cell lymphomas develop from B-cells located where?
Germinal center.
91
What happens in B-cell lymphomas?
When DNA breaks in *somatic mutation and isotype switching*, oncogenes translocate (sneak) in the Ig.
92
\_\_\_\_\_\_\_ may also contribute to autoimmunity.
Germinal center.
Somatic mutation can produce a self-reactive B cell clone in GC. Thus, SM is not perfect
93
Memory cells are made in the GC for ________ protein antigens.
T-dependent
94
Memory B cells are able to survive for long periods to time, without being stimulated by an antigen. How?
Express high levels of **Bcl-2**, an anti-apoptotic protein.
95
Do memory cells B cells have BCRs?
They have high affinity and Ig molecules are of switched isotypes (anitbodies other than IgM or IgD).
96
After secondary exposure to an antigen, antibody production \_\_\_\_\_\_\_\_\_\_\_
greatly increase thanks to the activation of memory cells.
97
fate of memory B cells
1. stay in **lymphoid organ**
2. recirculate between [**blood and lymphoid organ**].
98
What are TI (thymus independent) antigens?
Many **non-protein antigens,** stimulate antibody production in the absence of Th cells.
They are usually **low affinity** and mainly consist **IgM**, with *limited isotype* switching to some IgG subtypes and IgA
99
Properties of TD antigens
* Proteins
* Undergo isotype switching (IgM --\> IgG, IgA, IgE)
* Undergo affinity maturation
* Make memory B cells
100
Properties of TI antigens
* Non-proteins
* Low level of isotype switching
* Little or no affinity maturation
* Only some polysaccharide antigens make memory cells.
101
Most TI antigens are \_\_\_\_\_valent
**mutlvalent**
## Footnote
Thus, they have repeated identical epitopes--\> *cross-linking* of the BCRs--\> activation *without help* from T-cells.
102
TI Ab responses may be initiated where?
spleen, bone marrow, peritoneal cavity, and mucosal sites.
103
-The ________ and ________ are important for antibody responses to TI antigens.
MZ B cells
B1 B cells
104
MZ B cells in the spleen mainly respond to \_\_\_\_\_\_. After activation, they differentiate into what?
polysaccharides
short lived plasma cells--\> igM
105
B1 B-cells respond to TI antigens in the what?
peritoneum and mucosal sites
106
The most important TI antigens are what?
polysaccharides
glyolipids
nucleic acids
107
How do TI antigens (polysacharides, glycolipids and nucleic acids) activate B cells?
through polysaccharides activate the complement system via the alternative pathway C3b--\> [binds to antigen] --\> processed into C3d, which is recognized by CR2 on B cells.
-PAMP will activate TRL on B cell
108
What can stimulate isotype switching in T1 responses?
Some TI antigens can induce Ig isotype switching (other than IgM). GIve an example
1. Some TI antigens can cause Ig isotype switching.
Ex
pheumoccocal capsular polysaccharide induces IgG2.
2. Cytokines. Ex. TGF-B induces IgA switch
109
how do we produce AID?
DC and MO release BAFF.
This is facilitated by the activation of TLRs on B cells
110
How do TI Antibodies protext us?
TI antibodies are antibodies that are not released in response to a CD4+ T-helper cell.
1. Most TI antigens are **polysaccharides of encapsulated bacteria**. Humoral immunity is the major mechanism of defense against encapsulated bacteria. If people have immundeficiences of humoral immunity, they are susceptible to life bacterial infections.
2. TI antigens also make **NATURAL antibodies.**
111
What are natural antibodies?
Natural antibodies are present in the circulation of normal people without overt exposure to pathogens.
Most are l**ow affinity anti-carbohydrates** antibodies, made by peritoneal *B1 cells* in the GI tract and *MZ B-cells* in the spleen.
112
Effective vaccines against microbes and toxins must: _________ and \_\_\_\_\_\_\_\_\_
**cause affinity maturation** and
## Footnote
**form memory B cells.**
113
memory only occurs if the vaccine can do what
activate helper T-cells.
114
How do we make vaccines for capsulate polysaccharide , which ccannot stimulate T cells?
Polysaccharide is linked to a foreign protein to form a **hapten-carrier conjugate.**
They then bind MHC molecule and activate the TCR directly or function as an anchor for a sugar epitope.
Such vaccines, called **conjugate vaccine**s, more readily induce high-affinity Abs and memory cells
115
**Conjugate vaccines** induce long-lived protective immunity. How?
Rapid and large secondary repsonses similar to memory (but without much isotype switching or affinity maturation) may occur on secondary exposure to the carbohydrate antigens.
116
Why is B-cell activation is tightly controlled
to avoid collateral damage and prevent reactions against self-antigens
117
Inhibitory receptors structure
extracellular ligand binding domain and a cytosolic ITIM motif.
When a ligand binds, ITIM tyrosine is phosphorylated by Src family kinase.
118
Inhibitory r signaling on B cells
1. ligand binds
2. **Src family kinase** phosphorylates ITIM tyrosine.
3. **SH2 domain containing tyrosine phosphatases** bind to the p-ITIM and inhibit signal.
119
CD32 is also called?
FcyRIIB
120
What does FcyRIIB do?
1. Inhibitory receptor in B cells.
## Footnote
2. Attenuates signaling in activated DCs and macrophages
121
How are cells regulated by FcyRIIIB?
1. Ag-Ab complex binds to [BCR and FcyRIIB] via the Fc portion of the antibody.
2. Src kinases phosphorylate ITIM
3. p-ITIM recruits **SHP** and **SHIP** (tyrosine phosphotases with an SH2 domain)
4. **PIP3--\>PIP2**, blocks BCR signaling and activation by inhibiting PIP3 kinase activity in [*lymphocytes, NK cells, innate immune cells*]
122
What is antibody feedback?
Where a secreted antibody blocks the production of antibodies.
123
Purpose of antibody feedback
1. Stop the humeral immune response once we have enough IgG being made.
2. Prevents attacks to self antigens.
124
A polymorphism in in the gene that encodes FcyRIIB would lead to what?
Lupus erythematosus
125
[Q:] If a mice had a KO gene for FcyRIIB, what would we see?
Uncontrolled antibody production
126
We do not clear of situations where secreted antibodies provide compliment-mediated amplification or Fc receptor-mediated inhibition. What is a likely scenario?
A likely scenario is that IgM that activate compliment but do not bind to the FcyR are involved in amplication, wherease increasing production of IgG leads to feedback inhibition.
