Clonal Selection Theory Overview

Clonal Selection Theory

• Each lymphocyte uniquely expresses a single antigen receptor with specific targeting. The complete repertoire of lymphocytes can respond to any antigen.
• Lymphocyte activation requires binding to an antigen.
• Activated lymphocytes' progeny (effector cells) express identical receptors as the parent cell.
• Lymphocytes with receptors for self-antigens are either inactivated or eliminated.

Clonal Selection Theory: Tenets 1, 2, & 3

• Tenet 1: Each lymphocyte is clonotypic, distinct from other cells except its immediate precursors or progeny. This is due to the antigen receptor and its genetic origin. Large diversity of lymphocytes is generated due to rearranged genes.

• Tenet 2, 3: Receptor binding is crucial for lymphocyte activation. BCRs (B cell receptors) on the cell surface act with signalling molecules that recognize when an antigen is bound and activate the cell. This leads to antibody production and the cell's proliferation and differentiation. The B cell's clone and antibody's specificity are fixed by the initial receptor-generating rearrangement.

B Cell Receptor (BCR) Structure

• BCR consists of heavy (H) and light (L) chains.
• One H chain locus and two L chain loci (k and l).
• The H chain has V, D, and J gene segments.
• The L chain has V and J gene segments.
• Only one L chain type (k or l) is expressed per cell.
• H and L chains join to form the receptor. Heavy chains initially associate with the more 5' C-region genes (µ and δ).

B Cell Development

• Antigen-independent: B cell development in the bone marrow, except for negative selection.
  • Autoreactive B cells with strong self-antigen binding undergo apoptosis deletion.
  • Weaker binding may result in anergy(non-responsiveness).
• Antigen-dependent: B cell development in the periphery.
  • Antigen binding after leaving bone marrow can trigger IgM release.
  • Isotype switching and somatic hypermutation require T cell help. Occurs in germinal centers within lymph nodes.
• Isotype switching: Altering antibody class (e.g., IgM to IgG) while maintaining the same antigen specificity. Crucial for different immune functions.
• Somatic hypermutation: Mutations improve antigen binding within the antibody's variable regions, concentrated in hypervariable regions (CDRs). This occurs concurrently with isotype switching.
• Germinal centers: Specialized areas in lymph nodes where B cell proliferation and maturation happen, along with isotype switching and somatic hypermutation, via T-cell interactions.