Antibody class switching and affinity maturation are crucial processes in adaptive immunity. They allow B cells to produce different antibody types and improve their binding strength, enhancing the immune system's ability to fight diverse pathogens effectively.

These processes occur in germinal centers, where B cells undergo genetic changes. Class switching alters antibody types, while affinity maturation increases binding strength through mutations and selection, resulting in more effective immune responses over time.

Antibody Class Switching

Process of antibody class switching

• Antibody class switching alters B cell antibody production through isotype switching after activation
• Antibody classes include IgM, IgD, IgG, IgA, IgE with unique properties tailoring immune responses to specific pathogens (viruses, bacteria)
• Different isotypes affect tissue distribution and half-life of antibodies enhancing immune system versatility

Mechanisms of class switch recombination

• Class switch recombination (CSR) involves DNA recombination in activated B cells
• Activation-induced cytidine deaminase (AID) enzyme initiates process creating double-strand DNA breaks
• Non-homologous end joining (NHEJ) repair mechanism rejoins DNA strands
• Switch regions containing repetitive DNA sequences upstream of constant region genes facilitate recombination
• Cytokines produced by T helper cells direct switching to specific isotypes (IL-4 for IgE, IFN-γ for IgG2a in mice, TGF-β for IgA)

Affinity Maturation

Affinity maturation for high-affinity antibodies

• Affinity maturation improves antibody binding strength over time in germinal centers of secondary lymphoid organs (lymph nodes, spleen)
• Process enhances immune response effectiveness and improves pathogen clearance (influenza viruses, HIV)
• Key steps involve clonal expansion of activated B cells, somatic hypermutation, and selection of high-affinity B cell clones

Somatic hypermutation in germinal centers

• Somatic hypermutation introduces point mutations in variable regions of immunoglobulin genes at high rates
• AID enzyme mediates process in germinal center B cells
• Germinal center selection involves competitive antigen binding on follicular dendritic cells
• High-affinity B cells outcompete low-affinity cells for antigen binding and receive survival signals
• Low-affinity B cells undergo apoptosis through negative selection
• Process results in progressive increase in antibody affinity and generation of memory B cells and long-lived plasma cells