Clonal Selection Theory and B Cell Development

Clonal Selection Theory and B Cell Development

• Clonal selection theory explains the adaptive immune system's behavior
• Each lymphocyte has a unique antigen-specific receptor
• This receptor's binding is required for lymphocyte activation
• Effector cells have identical receptors to the parent cell
• Lymphocytes with receptors for self-molecules are inactivated or deleted
• B and T lymphocytes are clonotypic (unique)
• Diversity in antigen-specific receptors arises from somatic recombination (shuffling) in each cell
• This process creates a wider range of receptors than could be encoded in the genome, with progeny having identical receptors

B Cell Receptor Structure and Assembly

• B cell receptors (BCRs) are made of heavy (H) and light (L) chains
• One H chain locus and two L chain loci (kappa and lambda)
• Each locus contains multiple gene segments
• Germ-line gene configuration of Immunoglobin heavy- and light-chain loci
• H and L chains rearrange independently to form the receptor
• Initial expression involves the 5' most C region genes (e.g., IgM and IgD)

B Cell Receptor Expression

• Heavy (H) chains are formed from V, D, and J gene segments joined together
• Light (L) chains are formed from V and J gene segments joined to a C gene segment
• Both H and L chain rearrange independently and then pair

Clonal Selection Theory- Tenets 2 and 3

• Receptor binding is crucial for lymphocyte activation (recognition leads to action)
• BCRs are expressed on the cell surface together with non-polymorphic signaling molecules
• A signaling complex senses receptor binding and triggers intracellular activation
• Antibody production, proliferation, and differentiation occur
• B-cell clonotype and antibody specificity are determined by the genetic rearrangement of the receptor

Clonal Selection Theory- Tenet 4

• B cell development in bone marrow is mostly antigen-independent, except for negative selection
• Strong antigen binding at the immature B cell stage triggers apoptosis (deletion)
• Weaker binding can lead to anergy (unresponsiveness to antigen)

Antigen and T Cell-Dependent B Cell Development

• Antigen binding after leaving the bone marrow can cause the B cell to release IgM based on its cell surface receptor
• Isotype switching requires interaction with T cells ("T cell help")
• Isotype switching and somatic hypermutation occur in specialized germinal center structures in lymph nodes

Isotype Switching- Function

• Functionally, IgG, IgD, IgG1, IgG2, IgG3, IgG4, IgA, IgE are involved in neutralization, opsonization, etc.
• Distribution of the antibodies happens across different tissues (epithelial, placenta etc.)

Somatic Hypermutation- Antigen Binding

• Mutations within the H and L chain variable regions enhance antigen binding
• This process accumulates in "complementarity-determining regions (CDRs)" or "hypervariable" regions
• Occur in parallel to isotype switching

Isotype Switch and Somatic Hypermutation in Germinal Centers

• These processes occur within germinal centers within lymph nodes
• Proliferating B cells compete to present antigens and get T-cell help.

Summary of B Cell Development

• Somatic rearrangement is key to B cell receptor diversity
• Antigen-independent and antigen-dependent stages are involved in B cell development
• Some autoreactive B cells are deleted during the immature stage in the bone marrow
• Antigen binding triggers B cell activation
• Antibody specialization occurs through isotype switching and somatic hypermutation in germinal centers with T-cell help

This quiz explores the fundamentals of clonal selection theory and the development of B cells within the adaptive immune system. Learn about antigen-specific receptors, lymphocyte activation, and the unique composition of B cell receptors. Test your understanding of these crucial immunological concepts.