37 Questions
What is the primary function of the humoral immune response?
Production of immunoglobulins or antibodies
Where are antibodies mainly present in the body during an immune response?
Extracellular fluids
Which of the following is NOT a class of antibodies?
IgX
What does somatic hypermutation refer to in the context of B cell biology?
A mechanism introducing random mutations in antibody genes
Which cell type is responsible for somatic hypermutation?
Centroblast
What is the main outcome of affinity maturation in B cells?
Enhanced antibody specificity for antigens
Which signaling molecules downstream of the BCR pathway lead to B cell activation?
$ ext{NF-} ext{кB}$ and $ ext{PI3K}$
What is the role of follicular dendritic cells in B cell activation?
Promote survival and proliferation of germinal center B cells
What type of B cell is found in the follicles of the spleen and lymph nodes?
Follicular B cells
Which B cell type responds to non-protein antigens and rapidly produces IgM?
Marginal zone B cells
What is the outcome of B cell signaling for each B cell?
Clonal expansion
Where do activated B cells and TFH cells migrate to for primary focus of B cell clonal expansion?
Medulla
What type of B cells are known as centroblasts during rapid proliferation?
Follicular B cells
Which cytokines sustain proliferation of centroblasts in the germinal center?
IL-6, IL-15, BAFF
Where do some of the B lymphoblasts attached to TFH cells traffick back to for rapid proliferation?
Primary follicle
What is the primary mechanism responsible for the high rate of mutations in B cells during affinity maturation?
Action of AID
Which cells in the germinal center express a B cell receptor (BCR or sIg+) after completing somatic hypermutation?
Centrocytes
In affinity maturation, which type of cells test the BCRs for affinity to antigens?
Follicular dendritic cells
What is the main outcome of the interaction between centrocytes with high affinity BCRs and follicular dendritic cells (FDC)?
Survival signals for centrocytes
Which molecule is captured by Fc receptors on FDC during the process of affinity maturation?
IgM
What is the role of CD21 on centrocytes during interaction with antigens captured by FDC?
Stabilization of Ag binding
Which signaling mechanisms are essential for the survival of centrocytes during affinity maturation?
BCR and CR signaling
What is the final outcome for centrocytes with the highest affinity BCR for antigens?
Proliferation into plasma cells
What is the fate of centrocytes if they fail to interact with TFH cells and FDC?
Undergo apoptosis and are phagocytosed by tingible body macrophages
What signaling molecules promote the proliferation and differentiation of GC B cells into plasma cells?
IL-10 and IL-21
Where do long-lived plasma cells primarily reside in the body?
In the bone marrow
What is the main role of memory plasma cells?
Constantly secrete low levels of Ig
Where do short-lived plasma cells primarily originate?
Medulla
Which cells differentiate into long-lived plasma cells in the bone marrow?
Plasmablasts
What signaling molecules are associated with the BCR on B cells?
Igα and Igβ
Which kinase phosphorylates the immunoreceptor tyrosine-based activation motif (ITAM) on B cell receptors?
Lyn
What is the role of Syk in B cell activation signaling?
Binds to the PITAMs
Which component is NOT part of the B cell co-receptor?
CD3
What is the function of CD19 in B cell activation?
Enhances signaling pathways associated with BCR crosslinking
Which process results in an increase in BCR signaling events up to 10,000-fold?
Co-receptor activation
Patients lacking functional CD19 or CD81 components have low levels of serum antibodies due to:
Limited isotype switching
'Centrocytes' in germinal centers are characterized by:
'Light zone' morphology
Study Notes
B Cell Activation and Differentiation
Humoral Immune Response
- Produces immunoglobulins (antibodies) to combat pathogens
- Antibodies present in blood, lymph, and extracellular fluids
- Five classes of antibodies: IgM, IgD, IgA, IgE, and IgG, each with different functions
Types of B Cell Responses
- Follicular B cells: produce all types of antibodies, require T cell help, and are found in spleen and lymph node follicles
- Marginal zone (MZ) B cells: respond to non-protein antigens, rapidly produce IgM, and are localized to the marginal zone
- B-1 B cells: respond to non-protein antigens, rapidly produce IgM, and are found in fetal liver and adult bone marrow
B Cell Activation
- Requires three signals: BCR signaling, B cell co-receptor signaling, and cytokine signaling
- BCR signaling: crosslinking of BCR by antigen epitopes, leads to phosphorylation of ITAMs and activation of Syk and downstream signaling pathways
- B cell co-receptor signaling: CD19, CD81, and CR2 recognize and bind to antigen-bound IgG and C3d, enhancing BCR signaling
- Cytokine signaling: CD40-CD40L interactions and cytokines from T cells (IL-2, IL-4, IL-5) promote B cell activation and proliferation
Germinal Center Formation
- Activated B cells and TFH cells migrate to the medulla and undergo clonal expansion
- B cells differentiate into centroblasts, which undergo rapid proliferation and somatic hypermutation
- Centrocytes are generated, which express a BCR and undergo affinity maturation
- Centrocytes with high affinity BCR for antigen survive and differentiate into plasma cells
Plasma Cells
- Short-lived plasma cells: produce IgM, are formed in the medulla, and undergo apoptosis
- Long-lived plasma cells: produce IgG, are localized to inflamed tissues and bone marrow, and constantly secrete low levels of Ig
Memory B Cells
- Remain in blood circulation or reside transiently in lymphoid organs
- Do not produce Ig, but express a BCR
- Serve as a reservoir for memory B cell responses
Memory B Cell Development
- FDC capture, concentrate, and slowly release antigens
- BCR signaling induces movement of BCR to the site of antigen contact, promoting BCR crosslinking and activation
Signaling Molecules
- Igα and Igβ contain cytoplasmic tails with ITAMs
- Syk binds to the ITAMs and acts similar to ZAP-70 in T cells
- PLC and Ras/Rac pathways are activated, leading to transcription factor binding and activation signals
Test your knowledge on B cell activation and differentiation with this quiz focusing on the localization of naïve and activated B cells, the three signals required for B cell activation, chemokine receptor modulation, the roles of follicular dendritic cells, cytokines, CD40-CD40 ligand interactions, and activated induced deaminase.
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