Dr. M. Shimoda
Mechanisms of Disease, Lecture 5a
January 24th, 2006
- B Cell Development and Function
- B Cells
- Antibody Functions
- B-Cell Development and Differentiation
- Each B cell expresses B cell receptor (BCR) with a single specificity.
- On activation by antigen, B cells differentiate into plasma cells (which secrete antibody molecules, the soluble form of BCR, of the same antigen specificity as the BCR) and memory cells (which produce long-term immunity to the pathogen).
- B cells play a critical role in adaptive humoral immune response as antibody-producing cells, and as antigen-presenting cells which activate T cells.
- Activated B cells (lymphoblasts) can be recognized by their large, heterogeneous nucleus and widespread endoplasmic reticulum, resulting from an increased rate of translation required to produce large amounts of antibody.
- Neutralization by binding to small antigens, making them large enough for macrophages to phagocytize.
- Opsonization by coating a large pathogen with many antibody molecules to signal it for phagocytizing by macrophages.
- Complement activation by binding to a large pathogen and activating complement to lyse it prior to phagocytizing by macrophages.
- Antibodies are highly flexible, allowing antibody-antigen complexes to be formed between two antibodies (O° between arms), three antibodies (60°), and four (90°).
- Antibodies bind to antigens by noncovalent forces:
- Electrostatic attractions
- Hydrogen bonds
- Van der Waals forces
- Hydrophobic forces
- IgM and IgA can form multimers by combining at their constant regions with the assistance of a J chain.
- IgM forms a decavalent pentamer.
- In "staple" conformation, all five antibody moieties arch down to bind ten antigen moieties on a microbe, providing a larger docking site for complement than IgG would.
- IgA forms a tetravalent dimer.
- Membrane-bound BCR is a form of IgM.
- An Igδ (delta) and Igα (alpha) dimer associates with the constant region of BCR, transducing the binding signal through the membrane to Src-family kinases.
- Generation of B-cell receptors in bone marrow: B cell precursor rearranges its immunoglobulin genes (somatic recombination) and develops its specificity.
- Negative selection in bone marrow: Immature B cell bound to self cell-surface antigen is removed from the repertoire.
- B cells migrate to the peripheral lymphoid organs: Mature B cell bound to foreign antigen is activated.
- Antibody secretion and memory cells in bone marrow and lymphoid tissue: Activated B cells give rise to both plasma and memory cells.
- Early B-cell development is dependent on binding to bone-marrow stromal cells.
- Steps of rearrangement signal steps of B-cell development, ensuring that failed recombinants do not mature.
- Helper T cells stimulate the proliferation and then differentiation of B cells that recognize the same antigen.
- They also provide cytokines which promote isotype-switching.
- Germinal centers of lymph nodes are the site for both isotype-switching and for somatic mutations which alter B-cell specificity and affinity for its antigen.
Table of Contents
Back to MCG Class Notes Index