Lecture 26 - B cells Flashcards
What do TFH cells secrete?
IL-21 and cytokines typical of type 1 (IFN-γ), type 2 (IL-4), and type 3 (IL-17) responses.
What is the effect of TFH cell signaling on B cells?
Activates B cells to produce specific types of antibodies.
How do TFH cells interact with B cells?
They interact directly with B cells.
What type of pathogens do TFH cells respond to?
All types of pathogens.
What is IgM?
Immunoglobulin M — an antibody class that serves as a receptor on naïve B cells.
What cytokines are linked to type 1, type 2, and type 3 responses?
Type 1 → IFN-γ
Type 2 → IL-4
Type 3 → IL-17
What type of immune cell are B cells?
A type of lymphocyte.
Where do B cells arise from?
Bone marrow.
What role do B cells play in adaptive immunity?
- Antigen-specific
- Clonotypic (each B cell has a unique receptor)
- Progenitors of antibody-producing plasma cells and plasmablasts
What are plasma cells?
Activated and differentiated B cells that are the main antibody-secreting cells.
What are plasmablasts?
B cells in a lymph node that already show some features of plasma cells.
What happens to the B cell receptor when a B cell is activated?
It is secreted as an antibody.
What is clonal selection and expansion?
The process where an activated B cell proliferates and differentiates into plasma cells.
What is the outcome of B cell activation?
Plasma cells that secrete antibodies.
Where do naïve B cells circulate?
Through the lymph nodes and spleen regularly.
How do B cells enter the lymph node?
Through high endothelial venules (HEV).
What happens if a B cell doesn’t encounter an antigen?
- Leaves via efferent lymphatics
- If it doesn’t encounter an antigen after a few months, it dies by apoptosis.
What happens if a B cell encounters an antigen?
It receives a survival signal (Signal 1).
What type of molecule do B cells look for?
Antigens — NOT p:MHC (peptide-MHC complexes).
How do antigens reach the lymph node?
Via afferent lymphatics.
What can antigens be linked to?
Complement components (opsonized).
How are antigens retained in the lymph node?
By subcapsular sinus (SCS) macrophages and follicular dendritic cells.
What type of antigen enters the lymph node?
Opsonized antigen (bound to complement).
What cells in the lymph node retain opsonized antigen?
Subcapsular sinus (SCS) macrophages.
How do SCS macrophages retain opsonized antigen?
They express complement receptors that bind to complement on opsonized antigens.
Why don’t SCS macrophages degrade the antigen?
They have low endocytic and degradative activity.
Besides being retained by macrophages, how else can antigens exist in the lymph node?
Some antigens are free-floating in the lymph node.
How can B cells encounter antigen in the lymph node?
B cell receptors (BCR) bind specifically to an epitope on the antigen.
How can antigen be transported for later B cell differentiation?
Antigen can be transported onto the surface of follicular dendritic cells (FDCs).
What happens when an antigen (Ag) binds to the B cell receptor (BCR)?
It triggers signaling in the B cell.
What co-receptors are expressed by B cells?
CD19 and CD21 (complement receptors).
What do CD19 and CD21 bind to?
Complement proteins.
Is co-receptor binding necessary for BCR signaling?
No, but it can enhance signaling and activation.
What signaling subunits are associated with the BCR?
Igα and Igβ.
What motif do Igα and Igβ have, and what happens to it during signaling?
They have ITAM motifs that become phosphorylated.
How else can signaling be triggered besides BCR binding?
Through the co-receptor complex (CD19 and CD21).
What happens to ITAM motifs on Igα and Igβ during BCR signaling?
They become phosphorylated.
What are the three main outcomes of BCR signaling?
(1) Activation of transcription factors → gene transcription
(2) Survival signal
(3) Cytoskeletal reorganization
What happens to the BCR-antigen (BCR-Ag) complex after signaling begins?
It is internalized by the B cell (endocytosis).
What happens to the antigen after internalization?
It is processed and presented on MHC.
What can the presented pMHC interact with?
T cell receptor (TCR) on a T cell.
What provides Signal 2 for thymus-dependent (TD) antigens?
Activated CD4⁺ TFH cells.
What type of antibodies and immune response do TD antigens generate?
Specific antibodies and memory response.
What provides Signal 2 for thymus-independent (TI) antigens?
TLR (Toll-like receptor) signaling.
What kind of molecules are typically thymus-independent (TI) antigens?
Highly repetitive molecules, like LPS.
Which B cells respond to TI antigens?
B-1 and marginal zone B cells.
What type of antibody do B-1 and marginal zone B cells primarily produce?
IgM antibodies.
How does a TFH cell provide help to a B cell (Signal 2)?
(1) pMHC on B cell binds to TCR and co-receptor on TFH cell
(2) CD40 on B cell binds to CD40L on TFH cell
(3) Results in signaling and activation of transcription factors → B cell activation, proliferation, differentiation → antibody secretion
What other signals can TFH cells provide to B cells?
Cytokines.
How does the BCR recognize antigens?
The BCR can see the antigen in its natural form.
How does the TCR recognize antigens?
The TCR can only see small peptide fragments of the antigen bound to MHC molecules on the surface of Antigen-Presenting Cells (APCs).
What is linked recognition?
Linked recognition is the rule that for a TFH cell to activate a B cell, the epitopes recognized by the B cell and TFH cell must be derived from the same antigen.
How does the TFH cell recognize the antigen?
The TFH cell recognizes a peptide fragment of the antigen presented by MHC on an APC.
How does the B cell recognize the antigen?
The B cell recognizes the antigen in its native form, often from the surface of the pathogen (e.g., viral surface protein).
How do the epitopes recognized by the BCR and TCR differ?
The peptide recognized by the TFH TCR is likely to differ from the protein epitope recognized by the BCR.
Where is the epitope presented to the TFH cell?
On the surface of an APC, bound to MHC molecules.
What kind of antigen do B cells typically recognize?
B cells recognize the native structure of the antigen, such as a protein on the surface of a virus.
