Week 8 Lecture 2 B Cells and Antibodies

B Cells Overview

• B Lymphocytes (B Cells)

  • Primarily located in the spleen and lymph nodes, especially germinal centers.

  • Some circulate in the bloodstream.

  • Function is to secrete antibodies upon activation.

Specificity of B Cells

• Each B cell binds to only one specific epitope.

  • Example: A bacterium has multiple antigenic structures; B cells bind to specific subsets, not the entire antigen.

• B Cell Receptors (BCRs)

  • Define the specificity of B cells.

  • Structurally, BCRs are Y-shaped proteins similar to immunoglobulins, consisting of:

    • Two identical heavy chains (red).

    • Two identical light chains (pink).

    • All chains connected by disulfide linkages.

Structure of B Cell Receptors

• Y-Shaped Immunoglobulin

  • Each arm has a variable region that forms the antigen-binding site.

  • Unique for each B cell, determines the epitope it recognizes.

• Diversity of BCRs

  • Billions of possibilities due to unique generation during B cell development.

  • Each B cell receptor is unique, binding to only one specific antigen.

Genetic Mechanism for Diversity

• Gene Structure for Heavy Chain

  • Consists of three regions: variable (V), diversity (D), and junctional (J).

    • 65 variable segment options, 27 diversity segment options, 6 junctional segment options.

• Recombination Activating Gene (RAG)

  • Enzyme selects random combinations of V, D, and J segments during B cell maturation in red bone marrow.

  • This genetic splicing generates vast receptor diversity.

Analogy for Understanding Diversity

• Closet analogy: 65 types of shoes, 27 shirts, 6 pairs of pants allow for numerous outfit combinations.

  • Fire analogy represents RAG function that finalizes one of each type in the gene.

  • Two gene copies double the possibilities. Each B cell can potentially create billions of antibodies.

Activation of B Cells

• Encountering Antigen

  • Activation occurs when a B cell receptor binds to its specific antigen.

  • Results in:

    • Clonal expansion: B cell makes many copies.

    • Secretion of antibodies identical to BCRs.

• Plasma Cells

  • Activated B cells that secrete antibodies, rich in rough endoplasmic reticulum for protein synthesis.

Antibodies' Structure and Function

• Antibody Composition

  • Same structure as BCR with variable region and a conserved stem region (Fc region).

  • Unique variable region allows for specific binding; Fc region is uniform across all antibodies.

• Functions of Antibodies:

  1. Neutralization: Coats pathogens, preventing them from binding to cells.

  2. Opsonization: Antibody-coated pathogens are recognized and phagocytosed by immune cells.

  3. Oxidation: Production of harmful chemicals by antibodies to destroy pathogens.

  4. Agglutination: Binding two pathogens causes clumping, aiding immune clearance.

  5. Antibody-Dependent Cellular Cytotoxicity (ADCC): Anti-body-stimulated NK cells kill bound pathogens.

Summary

• B cells and antibodies are crucial components of the adaptive immune response.

• Their specificity and diversity are fundamental to effectively targeting and eliminating pathogens.

• Understanding these cells' roles helps elucidate the mechanisms of immune responses.