B-cell activation, differentiation, and memory

B-cell activation, differentiation, and memory

1. 2 Phases of Development

   • Antigen independent
     • Maturation: in bone marrow gene recombination and negative selection
       • heavy chain rearranges first and is expressed with a surrogate light chain
         • Non-functioning BCRs can be rescued by light chain rearrangement
       • Eliminates autoreactive B-Cells
   • Antigen dependent
     • Activation
       • 5 Steps of Activation
         • Step 1: Antigen binding BCR, must crosslink b/w multiple BCRs leads to signal 1
         • Step 2: Ag Presentation via MHCII, leads to TH activation
         • Step 3: Co-Stimulatory signals (CD40/CD40L) results in signal 2
         • Step 4: Cytokine Signaling, paracrine signaling from TH to B-Cell promotes activation
         • Step 5: Clonal B-Cell Expansion, Cell Cycle progresses to induce proliferation and clonal expansion
       • 2 Types
         • Thymus dependent
           • Direct Contact with T-H is required for signal 1&2
             • Signal 1 is from BCR antigen interaction and signal 2 is from MHCII and TCR interaction
         • Thymus independent
           • Antigen binding is able to induce both signals
     • Activation and Differentiation: Interaction with AG and T-H, clonal expansion into plasma and memory cells

2. Germinal Centers

   • B-Cell/T-Cell conjugates form in secondary lymphoid organs
   • Located in cortex

3. Affinity Maturation

   • Hypersomatic mutations occur after B-Cell Activation

4. B-Cell Class Switching

   • Cytokines direct effector function which causes class switching into various isotypes

5. Plasma and Memory Cells

   • Antibody production is increased in the medulla of the SLO
   • Memory cells enter a state of quiescence to sit and wait for further infection