T-Independent Antigens: Types & B Cell Activation

• Antigens can activate B cells without T cells assistance, these are separated into type one and type two antigens, activating via differing mechanisms.

Type 1 Antigens

• Some components of bacterial cell walls, such as LPS, act as T1 independent antigens.
• Act as polyclonal activators binding to surface structures other than BCRs
• They are typically lipopolysaccharides (LPS).
• They are often found in high abundance.
• Frequently referred to as B cell mitogens.

Type 2 Antigens

• Typically highly repetitious molecules like polymeric proteins or cell wall polysaccharide units.
• Contain repeating epitopes and are often multivalent polysaccharides.
• Activate B cells by extensively cross-linking membrane Ig receptors.
• Not considered mitogens.

B Cell Activation

• B cell activation can occur with or without T cells and via separate components of the microbial cell surface.
• Microbial surface proteins serve as PAMPs (pathogen-associated molecular patterns) accessible to immune cell receptors.
• T cell independent activation uses both BCRs and other surface receptors like TLR4 to recognize microbes, leading to activation and signal transduction.

Humoral Response to T Independent Antigens

• Weaker compared to T dependent antigens.
• No memory cells are formed.
• The predominant antibody formed is IgM.

T Independent Antigens Characteristics

• Repeating structures extensively cross-linking the B cell receptor, or cross-linking pattern recognition receptors and the B cell receptor together.
• Because T cells do not participate in the response to these T independent engines, there is no class switching.
• CD40 ligand on the surface of the T cell needs to interact with CD40 on the surface of the B cell to get class switching to IgG or IGA or IGE production , but without a T cell involved, class switching will not occur.
• Examples include bacterial lipopolysaccharides, capsular polysaccharides of bacteria, and polymeric proteins.
• The B cells can differentiate into plasma cells, but those plasma cells will only secrete the IgM class of antibody and tiny bits of IgD antibody as well, but they will not fast switch to produce IgG, IGA or IgE

T1 vs T2 Antigens

• T1 Antigens:
  • Nature: Simple, repetitive structures, like bacterial cell wall components (e.g., LPS).
  • Function: Directly activate B cells without T cell help, resulting in polyclonal activation.
  • Interaction: Efficiently cross-link multiple BCRs, triggering intracellular signaling pathways.
  • Immune Response: Predominantly induces IgM production with limited affinity maturation.
  • Examples: LPS from bacterial cell walls.
• T2 Antigens:
  • Nature: Complex molecules with repeating subunits, often derived from large pathogens or synthetic antigens.
  • Function: Directly activates B cells without T cell assistance, and can induce affinity maturation.
  • Interaction: Cross-link BCRs and may provide additional co-stimulatory signals.
  • Immune Response: Can induce both IgM and class-switched antibodies (e.g., IgG) with affinity maturation.
  • Examples: Polysaccharide-protein conjugates like Hib and pneumococcal conjugate vaccines.

Mechanisms of T Cell Independent B Cell Activation

• Common Aspects:
  • Direct BCR Interaction: Both T1 and T2 antigens directly engage BCRs on B cell surfaces.
  • Co-Receptors: CD19 and CD21 enhance B cell activation by binding complement-coated antigens.
  • BCR Cross-Linking: Cross-linking of BCRs induces intracellular signaling.
• T1 Antigens:
  • Polyclonal Activation: May lead to polyclonal activation of B cells.
  • IgM Dominance: Predominantly induces IgM antibody production.
• T2 Antigens:
  • Additional Co-Stimulation: May provide additional co-stimulatory signals for enhanced B cell activation.
  • Affinity Maturation: Some T2 antigens can induce affinity maturation.
  • Class-Switched Antibodies: Induces production of class-switched antibodies like IgG.
• Limitations Compared to T-Cell Dependent Activation:
  • Memory B Cell Formation: Less efficient induction of memory B cells.
  • Isotype Switching: Limited ability to induce class-switching.
  • Affinity Maturation: Generally limited compared to T-cell dependent responses.
  • Immune Memory: Often less robust establishment of long-term immune memory.