March 17 - B Cells I

What is signal 1 for B cells?

p:BCR

What is signal 2 for B cells?

TCR:pMHC II and CD40L and CD40

What are the additional signals for B cells?

Cytokines

What types of cytokines do T cells secrete for B cells?

IL-21 and cytokines typical of type 1, type 2 or type 3 responses.

What do these (cytokines) from T cells cause?

Triggers B cell to produce specific types of antibodies

What is IgM?

Immunoglobulin M - an antibody class that serves as a receptor on naive B cells.

Where do B cells arise?

In the bone marrow

What is the key role in adaptive immunity of B cells?

• Antigen-specific

• B cells are clonotypic

• Progenitors of antibody-producing plasma cells and plasmablasts

What are plasma cell characteristics?

Activated and differentiated B cells and the main antibody-secreting cells

What are plasmablast characteristics?

B cells in a lymph node that already show some features of plasma cells

What are the two types of B cell receptors?

B cell receptor is membrane bound and when the B cell is activated they secrete a B cell receptor (antibody)

How does clonal selection and expansion for B cells happen?

Activated B cells undergo proliferation and differentiation. There is a test in the bone marrow for B cells to see which are autoreactive. The outcome of clonal selection is that the plasma cell secretes antibodies

How do naive B cells enter into secondary lymphoid organs?

Enter lymph node through HEV

What happens if the B cell does not encounter Ag in a lymph node?

Leaves via efferent lymphatics, if it does not encounter Ag for months, B cell dies via apoptosis

What do B cells look for?

Antigen not p:MHC

If the B cell does encounter the antigen, what happens?

Provides a survival signal (signal 1)

How do the antigens from pathogens arrive in lymph nodes?

Afferent lymphatics

How can antigens be presented to B cells in the lymph node?

Covalently linked to complement compounds (opsonized) and Ag can then be retained in the lymph node by SCS macrophages and follicular dendritic cells

What happens once an opsonized antigen enters lymph node?

In lymph node → subcapsular capsule macrophage (SCS macrophage)

• Express complement receptor on their surface

• Can bind the complement on the opsonized antigen and retain that antigen in the lymph node

What can SCS macrophages do?

SCS macrophages retain antigen on their surface in lymph node

• These macrophages have low endocytic and degradative activity

What else can be free floating in the lymph node?

Some antigens are free floating in the lymph node as well

What can B cells entering the lymph node bind to?

BCR binds specifically to an epitope on Ag

Where can Ag be transported on?

The surface of follicular DC → important for later stages in B cell differentiation

What does the BCR bind?

BCR binds Ag

What does the B cell express other than BCR?

Co-receptor complement receptors (CD19 and CD21)

• Binds complement protein

• Not necessary but can enhance signaling and activation

What is BCR associated with and what are their characteristics? Which signaling subunits?

Associated with signaling subunits Igalpha and Igbeta.

These have ITAMs that can become phosphorylated, signaling can also occur via the co-receptor complex

What happens when phosphorylation of ITAMs Igalpha and Igbeta occurs?

Multiple signaling pathways are activated

What are the main outcomes of signal 1?

1. Transcription factors are activated → gene transcription

2. Survival signal

3. Cytokskeletal reorganization

Endocytosis of BCR-Ag

Once signaling begins what happens to BCR-Ag?

BCR-Ag complexes are internalized, internalized Ag are processed and presented on MHC, this pMHC can then interact with TCR on a T cell

What is the more common type of signal 2 for B cells?

Thymus-dependent antigens (TD antigens)

What are the characteristics of TD antigens?

• Signal 2 is provided by activated CD4+ TFH cell

• Specific Ab and provide memory

What are the characteristics of thymus-independent antigens (TI antigens)?

• Signal 2 is provided by TLR signaling

• Such Ag are typically highly repetitive molecules, such as LPS

Which B cells use TI antigens?

B-1 and marginal zone B cells (less diversity and give rise primarily to IgM antibodies)

What are the signals for TFH signal 2 for B cells?

• Signal from pMHC that has bound to TCR and co-receptor on the TFH cell

• Signal from CD40 on B cells that has bound to CD40L on TFH cell

What does signal 2 from TFH lead to?

Results in signaling and activation of transcription factors. Leads to activation, proliferation, differentiation → antibody secretion. Cytokines are other signals

What is the difference between the BCR and TCR recognizing the antigen?

BCR can see Ag in its natural form

The TCR can only see small pieces from the Ag bound to molecules of the MHC on the surface of APCs

What does the follicular helper cell need to be able to activate a B cell?

The epitopes recognized by the B cell and the follicular helper T cell have to be derived from the same antigen

What is the difference in the linked recognition peptide and antigen?

TFH recognize fragment of the same antigen as is recognized by the B cell

• Peptide recognized by the TFH cell is likely to differ from the protein epitope recognized by the BCR

• Peptide is processed and presented to TFH TCR vs the natural form for B cell’s BCR

What does the B cell vs T cell recognize?

• T cell recognizes epitope presented on MHC on DC (Could be from inside)

• B cell recognizes epitope (surface likely)