HI13 - B Cells and Antibodies Part 2

Biomedical Sciences IV

What triggers B cell activation?

Binding of antigen to the B Cell Receptor (BCR), along with signals from co-receptors and CD4⁺ T cells.

Where are mature naïve B cells located before activation?

In secondary lymphoid follicles, where they receive BAFF and other survival signals from follicular dendritic cells (FDCs).

What immunoglobulins do mature naïve B cells express?

Both IgM and IgD (via RNA-based, reversible splicing).

What happens when a mature naïve B cell meets its antigen and receives T cell help?

It proliferates, undergoes isotype switching, and differentiates into plasma or memory cells.

What is the first step in B cell activation?

Antigen crosslinking of BCRs (usually IgM) on the B cell surface.

What happens when BCRs are crosslinked?

Signal transduction occurs through CD79 ITAM phosphorylation, leading to changes in gene expression.

Is BCR signaling alone sufficient for full activation?

No, co-receptor engagement and T cell help are also required.

What is the B cell co-receptor complex made of?

CR2 (CD21), CD19, and CD81.

What complement component binds the B cell co-receptor?

C3d (or iC3b), which enhances activation.

What does CD19 do in the co-receptor complex?

Amplifies the intracellular signaling from the BCR.

How much does co-receptor engagement amplify the BCR signal?

By 1,000–10,000×.

Where does B cell and T cell interaction occur?

At the T–B cell boundary in secondary lymphoid tissue.

What chemokine recruits B cells to the follicle?

CXCL13, produced by FDCs.

What type of T cells help activate B cells?

CD4⁺ T follicular helper (Tfh) cells.

How are CD4⁺ Tfh cells activated?

By dendritic cells in the T cell zone presenting antigen on MHC II.

How do B cells present antigen to Tfh cells?

B cells internalize antigen, process it, and present peptides on MHC Class II.

What forms between the B cell and the Tfh cell during activation?

An immunological synapse.

What receptor–ligand pair is essential for B cell activation?

CD40 (on B cell) binding to CD40L (on Tfh cell).

What transcription factor is activated by CD40 signaling?

NFκB, promoting survival and proliferation.

What cytokine from Tfh cells promotes B cell proliferation and differentiation?

Interleukin-4 (IL-4).

What are the two possible fates of an activated B cell?

1) Differentiate into IgM-secreting plasma cells, or
2) Return to the follicle to form a germinal center.

What occurs in germinal centers (GCs)?

Somatic hypermutation, affinity maturation, and class switching.

What is the function of plasma cells in the medullary cords?

They secrete IgM antibodies to fight the current infection.

What is the function of memory B cells?

They persist long-term and can rapidly respond upon re-exposure to antigen.

What happens if a person lacks CD40 ligand (CD40L)?

They develop Hyper-IgM Syndrome. (There is no class switching, so only IgM is produced).

What are symptoms of Hyper-IgM Syndrome?

High IgM, very low IgG and IgA, no germinal centers, and poor antibody responses.

What type of inheritance does Hyper-IgM Syndrome have?

X-linked, primarily affecting males.

In how many waves are antibodies produced?

In two waves.

What is produced during the first wave?

IgM antibodies from short-lived plasma cells in the medullary cords.

What is the first site of antibody production called?

The primary focus.

Does the first wave include class switching or affinity maturation?

No, only IgM is produced.

Which cytokine promotes plasma cell differentiation?

IL-10.

Which cytokine promotes memory B cell differentiation?

IL-4.

What happens between the two waves of antibody production?

Some B–T cell pairs return to the follicle to form germinal centers.

What is produced during the second wave?

High-affinity, class-switched antibodies (e.g., IgG, IgA, IgE).

What cells are required for germinal center formation?

FDCs and Tfh cells.

What enzyme initiates somatic hypermutation and class switching?

AID (Activation-Induced Cytidine Deaminase).

What does AID do?

Deaminates cytosine to uracil in DNA, creating mutations that enable class switching and affinity maturation.

What are the two processes that occur in germinal centers?

Somatic hypermutation and isotype class switching.

What is the result of germinal center activity?

Expansion of antigen-specific B cells and swollen lymph nodes.

What is somatic hypermutation?

DNA-based point mutations in antibody variable regions that refine antigen binding after antigen exposure.

What is affinity maturation?

Selection of B cells with improved antigen affinity after somatic hypermutation.

Are somatic hypermutation and affinity maturation reversible?

No, both are DNA-based and irreversible.

Which high-affinity B cells survive during affinity maturation?

Those that bind antigen on FDCs and receive Tfh help survive.

What happens to low-affinity B cells in germinal centers?

They die by apoptosis due to lack of survival signals.

How many antibody classes are there?

Five: IgM, IgG, IgA, IgD, and IgE.

What process changes one antibody class to another?

Class switching (isotype switching).

Is class switching DNA- or RNA-based?

DNA-based and irreversible.

What enzyme drives class switching?

AID (Activation-Induced Cytidine Deaminase).

What cytokines promote IgG1 switching (TH1)?

Interferon-gamma (IFN-γ).

What cytokines promote IgG2, IgG4, IgA, and IgE switching (TH2)?

IL-4 and IL-5.

What is the purpose of class switching?

To produce antibody isotypes with different effector functions suited to various immune responses.

What is the first antibody made during infection?

IgM.

What is the structure of IgM?

A pentamer with 10 antigen-binding sites.

What is the main function of IgM?

Complement activation via the classical pathway.

Why doesn’t IgM diffuse into tissues?

It’s large and stays mainly in the bloodstream.

What is the most abundant antibody in serum?

IgG (80–85% of serum antibodies).

What is IgG’s half-life?

About 21 days.

What are IgG’s key functions?

Opsonization, complement activation, neutralization, ADCC, immobilization, and cross-linking.

Which antibody crosses the placenta?

IgG (via the FcRn receptor).

How long does maternal IgG protect infants?

Up to 6 months after birth.

What is the main antibody in mucosal secretions?

IgA (mainly dimeric).

Where is IgA found?

In saliva, TEARS, mucus, and breast milk.

What are IgA’s main functions?

Neutralization and prevention of pathogen adherence.

How is secretory IgA transported across epithelium?

Via the poly-Ig receptor and secretory component.

What is known about IgD’s function?

It likely aids in B cell activation and may protect the respiratory tract.

How abundant is IgD in serum?

It’s the least abundant (~1%).

Where is most IgE found?

Bound to mast cells, basophils, and eosinophils via FcεRI receptors.

What happens when antigens crosslink IgE on mast cells?

Degranulation and release of histamine and inflammatory mediators.

What are the primary roles of IgE?

Defense against parasites and helminths, and mediation of allergic reactions.

Which antibody predominates in the bloodstream?

IgG and monomeric IgA.

Which antibody predominates in mucosal secretions?

Dimeric IgA.

Which antibody predominates in early responses to infection?

IgM.

Which antibody protects the fetus and newborn?

IgG (via placenta and colostrum).

Which antibody is associated with allergic reactions?

IgE, found beneath epithelial surfaces.

Do all B cells require T cell help?

No, some can be activated T cell–independently.

What are T cell–independent (TI) antigens?

Repetitive polysaccharides, bacterial cell wall components, and high-density epitopes.

Which B cell type typically recognizes TI antigens?

B-1 B cells.

Do TI responses form germinal centers?

No, they do not.

Do TI responses undergo class switching or affinity maturation?

No, they produce only IgM antibodies.