B cell activation and Antibody Effector Function - Unit 2

What is the first step required for B cell activation?

Cross-linking of the B cell receptor (BCR) — the surface immunoglobulin — by binding two identical epitopes on the same antigen.

Why is BCR cross-linking necessary for B cell activation?

It initiates intracellular signaling pathways that activate the B cell.

What facilitates BCR cross-linking on the B cell surface?

B cell co-receptors that enhance antigen binding and signal amplification.

Where in the lymph node are antigens first displayed to B cells?

In the primary follicles by follicular dendritic cells (FDCs).

What is the role of follicular dendritic cells (FDCs) in B cell activation?

They trap and retain antigens from lymph for extended periods, allowing B cells to recognize and bind them.

What T cell type provides help to B cells during activation?

Follicular helper T cells (T_FH).

How do T_FH cells become specific for the same antigen as B cells?

They are previously activated by myeloid dendritic cells presenting the same antigen.

After activation, where do T_FH cells migrate in the lymph node?

To the boundary between the follicle and the T cell area.

What happens when activated B cells encounter T_FH cells at the follicle boundary?

B cells present antigen on MHC-II to the T_FH cell.

What defines a cognate pair in B cell activation?

A B cell and T_FH cell that recognize epitopes from the same antigen.

What molecules connect the cognate B and T_FH cells?

CD40 on the B cell and CD40L (ligand) on the T cell.

What do T_FH cells secrete after forming a cognate pair?

Cytokines that further activate and direct B cell differentiation.

Where do cognate B–T cell pairs migrate after interaction?

To the medullary cords of the lymph node.

What occurs at the medullary cords during B cell activation?

B cells divide to form the primary focus of plasma cell production.

What antibody type do plasma cells in the primary focus secrete?

IgM, the first antibody produced during infection.

Where do some B–T cognate pairs migrate after the medullary cords?

Back to primary follicles to form germinal centers.

What two cell types are found in germinal centers during the B cell response?

Centroblasts and centrocytes, which are rapidly dividing B cells.

What induces somatic hypermutation and isotype switching in germinal centers?

Cytokines secreted by T_FH cells.

Why do lymph nodes swell about one week after infection?

Due to the expansion of B cells within germinal centers.

How do centrocytes compete in germinal centers?

They compete for antigen held by FDCs; those with highest-affinity receptors survive.

What determines which antibody isotype a B cell switches to?

Cytokines produced by T_FH cells, which depend on the infection type and T cell activation context.

What cytokine induces plasma cell differentiation at the height of infection?

IL-10, secreted by T_FH cells.

What cytokine promotes memory B cell differentiation near the end of infection?

IL-4, secreted by T_FH cells.

Where do long-lived memory B cells reside after differentiation?

In the bone marrow, remaining dormant until reactivation by the same antigen.

What are the main functions of follicular helper T (T_FH) cells?

Provide B cell help through CD40L–CD40 signaling and cytokine secretion to promote proliferation, isotype switching, and affinity maturation.

How do T_FH cells promote somatic hypermutation and isotype switching?

By secreting cytokines like IL-21, IL-4, and IL-10 that act on germinal center B cells.

What determines whether a B cell becomes a plasma or memory cell?

The cytokines secreted by the interacting T_FH cell (IL-10 for plasma, IL-4 for memory).

Which immunoglobulins protect internal tissues?

IgM, IgG, and monomeric IgA.

What are the main features of IgM?

Produced early in infection; pentameric structure with 10 binding sites but low affinity.

How does IgG provide tissue protection?

Small size and high affinity; crosses endothelium via FcRn receptors without lysosomal degradation.

What is the main role of monomeric IgA in the blood?

High-affinity pathogen neutralization in circulation.

Which Ig protects mucosal surfaces?

Dimeric IgA.

Where is dimeric IgA produced and secreted?

In mucosal-associated lymphoid tissue (MALT) beneath epithelial layers.

How does dimeric IgA cross epithelial barriers?

Binds poly-Ig receptor on the basolateral surface and is transported via transcytosis, leaving a secretory component attached.

Which antibody mediates rapid expulsion of parasites?

IgE.

How does IgE trigger immune defense?

Binds FcεRI on mast cells, basophils, and eosinophils, leading to histamine and mediator release upon cross-linking.

What type of immunity is conferred by maternal antibodies?

Passive immunity.

How is IgG transferred from mother to fetus?

Via FcRn-mediated transport across the placenta.

Which antibody in breast milk provides mucosal protection to infants?

Dimeric IgA.

What is the function of neutralizing antibodies?

Block pathogen or toxin attachment to host cells by binding surface proteins used for entry.

Give an example of neutralizing antibody action.

Anti-hemagglutinin antibodies blocking influenza virus binding to respiratory cells.

What is agglutination and which Ig mediates it?

Clumping of antigens or cells by antibody binding; typically mediated by IgM.

How can agglutination cause a transfusion reaction?

IgM binds ABO antigens on RBCs, causing clumping and vessel blockage.

Which immunoglobulins activate complement by the classical pathway?

IgM and IgG.

How does IgM activate complement?

Binding to pathogen surface changes its conformation, allowing C1 complex attachment and C3 convertase formation.

How are immune complexes cleared from circulation?

RBCs express complement receptor CR1, bind C3b-tagged complexes, and transport them to liver/spleen macrophages for removal.

What is opsonization?

Antibody-mediated enhancement of phagocytosis via Fc receptor recognition.

Which Fc receptor is involved in opsonization by IgG?

FcγRI on macrophages, monocytes, dendritic cells, and neutrophils.

What process do opsonized pathogens undergo inside phagocytes?

Engulfment into a phagosome, fusion with lysosomes, and destruction.

How does antibody-dependent cell-mediated cytotoxicity (ADCC) occur?

NK cells use FcγRIII to bind IgG-coated target cells and induce cytotoxic killing.

Which cells are typically targeted by ADCC?

Virus-infected or tumor cells coated with IgG.

Give a clinical example of ADCC.

Rituximab-mediated destruction of CD20⁺ B cells in lymphoma.