B Cell Activation and Effector Functions

B Cell Activation and Isotype Switching

• B cells are activated by antigen presented by MHC and co-stimulatory (CD40-CD40L) signals from Th2 cells.
• After activation, B cells undergo rounds of mutation and selection to generate high-affinity memory B cells and plasma cells.
• Plasma cells are B cells that secrete their antigen-specific receptors in the form of antibodies.

Used with permission from Macmillan Publishers Ltd: Nature Reviews Immunology 2, 60-65, copyright 2002.

• B cells are similar to T cells in that they undergo somatic hypermutation to produce their antigen receptors. However, B cells also undergo a process called isotype switching which allows different functional classes of antibodies (i.e., IgM and IgG) to be produced that all have the same antigen specificity.
• Isotypedetermines the effector function of the antibody.
  • Antibodies are originally of the IgM isotype.
  • When activated B cells are exposed to IL-4, they undergo isotype switching to IgE.
  • When activated B cells are exposed to TGF-beta, they undergo isotype switching to IgG2b and IgA.
  • When activated B cells are exposed to IFN-gamma, they undergo isotype switching to IgG2a and IgG3.

Antibody Effector Functions

• Antibodies bind to extracellular pathogens and toxins to mediate their destruction by phagocytic cells.
• There are 4 main methods by which antibodies exert their effects

Used with permission from Macmillan Publishers Ltd: Nature 421, 440-444, copyright 2003.

1. Neutralization occurs when antibodies bind to pathogens or toxins in order to prevent the pathogens from infecting cells.
2. Opsonization 
   • Antibodies contain both a Fab region, which is specific for the antigen, and an Fc region, or constant region. When a bacterium or toxin is covered with antibodies, the Fc region of these antibodies can be recognized by phagocytic cells during the process of opsonization.
   • Note: This is one of the main effector mechanisms responsible for the efficacy of anti-CD20 and anti-CD52 monoclonal antibodies. When these antibodies bind to cancer cells expressing CD20 or CD52, they induce opsonization, which leads to the death of the cancer cells.   
    
3. Complement Activation
   • Complement is a system of plasma proteins that can be activated by antibodies bound on a cell. The complement cascade leads to the formation of a protein complex on bacteria that can kill the bacteria. The complement system can also activate phagocytes to destroy bacteria that would otherwise not be recognized by the immune system.  
    
4. Antibody-Dependent Cellular Cytotoxicity (ADCC)
   • ADCC occurs when the Fc portion of an antibody bound to the surface of a cell interacts with Fc receptor on immune cells such as macrophages, NK cells and neutrophils. This triggers the immune cell to target the antibody-coated cell for lysis.