Generation of antibody

• Describe B cell development

  B cells develop in the bone marrow, where stromal cells are involved in the rearrangement of immunoglobulin genes. B cells then express their rearranged immunoglobulin on the membrane surface as IgM class. If any of these interact strongly with self antigens in the bone marrow they are eliminated. Once B cells have matured they begin to express IgD and enter the lymph nodes.
• Describe B cell activation

  B cells usually require 2 signals to become activated:

  • Signal 1: recognition of antigen by membrane immunoglobulin molecule.
  • Signal 2: most often from interacting with CD4+ T cell
• How and where are B cells activated?

  1. Antigens are carried by dendritic cells from the tissue and drain into the lymph node, specifically the marginal zone.
  2. DCs migrate through the cortex region of the lymph node and present antigen to B cells.
  3. B cells that recognise the antigen by the IgM receptor will migrate to the border between the cortex and paracortex to meet with T cells.
• What happens to B cells at the cortex/paracortex border?

  B cells become activated and migrate to the medullary cords to form primary foci and some form the germinal centre in the primary follicle. B cells internalise the antigen and process it to present in on MHC II molecules to CD4+ T cells, which delivers the second activation signal to the B cell.
• What happens to CD4+ T cells following binding of antigen-MHC complex?

  Once the T cell adheres to the B cell it begins synthesising IL-4 and CD40 ligand. The T cell then reorientates its cytoskeleton and secretory apparatus towards the B cell. IL-4 is released, which is essential for B cell secretion of IgE and promotes T cell growth. Co-stimulatory molecules and cytokines stimulate clonal expansion and differentiation of B cells.
• What are FDCs?

  These are follicular dendritic cells that are designed to holding antigen antibody complexes on their surfaces in little nodules known as iccosomes throughout the primary follicle.
• Describe the structure of the germinal centre

  Dark zone: centroblasts- proliferating B cells

  Basal light zone: centrocytes

  Apical light zone: proliferating B and T cells

  • B cells enter the primary follicles and downregulate IG receptor expression and proliferate to form centroblasts. During this proliferation they undergo affinity maturation, where the H and L chains are hyper mutated In the variable region.

  
• Describe clonal selection within the germinal centre

  Centroblasts stop proliferating and re-express their IG molecule to form centrocytes, that move over the FDCs and if they bind to antigen with enough affinity they receive a survival signal. As the immune process progresses, antigen levels fall and the centre types compete for less and less antigen so that only the highest affinity is selected.
• Describe how cytokines influence Ig class switching

  • No CD40: only IgM can be made
  • IL-4 induces IgE
  • TGF-beta induces IgA
• Describe the formation of memory and plasma cells

  B cells interact with CD4+ T follicular helper cells in apical light zone, which turns the B cell into a memory or plasma cell.