6.3 B cell activation and differentiation

B cell activation is a crucial process in the adaptive immune response. It involves two main pathways: T-dependent and T-independent activation, each triggering different mechanisms to combat pathogens and produce antibodies.

The activation process leads to the formation of germinal centers, where B cells undergo important changes. These include somatic hypermutation for improved antibody affinity and class switching to produce different antibody isotypes, ultimately resulting in diverse effector B cells.

B Cell Activation and Differentiation

T-dependent vs T-independent activation

• T-dependent activation requires T cell help involving protein antigens occurring in secondary lymphoid organs (lymph nodes, spleen)
• T-independent activation bypasses T cell help with two types: TI-1 and TI-2
  • TI-1 antigens like lipopolysaccharides (LPS) activate B cells via Toll-like receptors
  • TI-2 antigens such as polysaccharides with repetitive structures crosslink multiple B cell receptors

Role of T helper cells

• T helper cells provide co-stimulatory signals and secrete cytokines
• CD40L-CD40 interaction promotes B cell survival and proliferation
• Cytokines influence B cell fate:
  1. IL-4 promotes class switching to IgE
  2. IFN-γ induces class switching to IgG2a
  3. TGF-β stimulates class switching to IgA
• Cytokines guide differentiation into plasma or memory cells

Germinal center formation

• Structure divided into dark and light zones
  • Dark zone: Centroblasts undergo rapid proliferation
  • Light zone: Centrocytes interact with follicular dendritic cells and T cells
• Somatic hypermutation in dark zone introduces mutations in antibody variable regions
• Affinity maturation in light zone selects B cells with high-affinity antibodies
• Class switch recombination changes antibody isotype without altering antigen specificity

Types of effector B cells

• Plasma cells secrete large quantities of antibodies
  • Short-lived plasma cells reside in secondary lymphoid organs
  • Long-lived plasma cells migrate to bone marrow
• Memory B cells provide rapid response upon secondary antigen exposure
• Effector B cells produce antibodies, present antigens to T cells, and secrete cytokines
• Regulatory B cells produce IL-10 and TGF-β suppressing excessive immune responses