B Cell Biology and Antibody Production

B Cell Biology and Antibody Production

Lecture Objectives

Revise fundamental aspects of B cell biology (stuff you should already know).
Appraise the importance and uses of antibodies in immunology and medical science.
Dissect the biochemical events underlying B cell signaling and assess functional consequences.
Compare and contrast T cell-independent and T cell-dependent antibody responses.
Focus on the kinetics and cellular events underlying T cell-dependent antibody responses.

Fundamental Aspects of B Cell Biology

Clonal selection theory
Antibody differentiation into plasma cells
Structure and function of antibodies
Antibody recognition of antigen
Five isotypes (classes) of antibodies

Adaptive Humoral Immunity Definition

The form of adaptive immunity mediated by B lymphocytes.

B Lymphocytes

Adaptive immune cells that develop and differentiate in the bone marrow.
Morphologically identical to T cells under a microscope.
Activated B cells display a B cell receptor (BCR) on their surface.
BCR recognition of antigen leads to B cell activation, proliferation, and differentiation into effector B cells.

Plasma Cells

Terminally differentiated effector B cells.
Long-lived cells residing in the bone marrow, spleen, and lymph nodes.
Secrete soluble form of the BCR known as antibody.
Antibodies neutralize pathogens and possess potent antimicrobial activity.

Innate vs. Adaptive Immune Systems

Innate immune system is critical early in infection.
Adaptive immune system (B and T cells) takes over if the innate system is overwhelmed.
Lymphocytes (B and T cells) are critical components of the adaptive immune system.

B Cells vs. T Cells

B cells: bone marrow-dependent, responsible for humoral immunity.
T cells: thymus-dependent, responsible for cellular immunity.

Antigen Receptor Specificity

Each lymphocyte clone (B or T cell) expresses a unique antigen receptor with exquisite specificity for antigen.
Different from innate immune cells that express pattern recognition receptors (not antigen-specific).

Lymphocyte Activation and Differentiation

Resting lymphocytes (T and B cells) are morphologically indistinguishable.
Upon antigen receptor recognition, lymphocytes become lymphoblasts, increasing in size with an enlarged nucleus.
Lymphoblasts divide and differentiate into effector cells (e.g., plasma cells for B cells).
Plasma cells have a highly developed endoplasmic reticulum.

Clonal Selection Theory

During differentiation in primary lymphoid organs, a vast array of lymphocyte clones is generated, each with a unique specificity.
This process is independent of foreign antigen.
In an immune response, only clones specific for a given antigen are selected for.
These selected lymphocytes clonally expand and differentiate to become effector cells.

Memory and Specificity in Adaptive Immune Response

Exposure to antigen X leads to an immune response.
Subsequent exposure to antigen X results in a quicker and stronger secondary immune response.
The secondary response is antigen-specific; exposure to a new antigen Y elicits a primary response.

Antigen Receptor Differences Between B Cells and T Cells

T cell receptor (TCR) recognizes peptide and MHC.
B cell receptor (BCR) recognizes free antigen.
Both have variable and constant domains.
B cells have heavy and light chains; T cell receptors have alpha and beta chains.
Antigen receptor genes for B cells and T cells are distinct.

B Cell Receptor (BCR) Structure

Surface-bound antibody.
Consists of two identical heavy chains and two identical light chains.
Naive B cells express IgM and IgD as their BCR.

BCR vs. Soluble Antibody

The key difference is the transmembrane domain in the BCR, which anchors the antibody to the B cell surface.

Antigen Binding Site

Heavy and light chains have variable domains.
Complementarity Determining Regions (CDRs): Three on the light chain, three on the heavy chain.
The six CDRs come together to form the antigen-binding site.
BCR recognizes free antigen, unlike TCR which requires peptide in the context of MHC.

Antibody Classes (Isotypes)

Five different classes (IgA, IgD, IgE, IgG, IgM) with different heavy chains and constant regions.
IgA: Principal antibody in mucosal systems.
IgD: Found on the surface of naive B cells as part of the BCR.
IgE: Specialized in defense against worms.
IgG: Major antibody found in serum.
IgM: Important early in infections and also found on the surface of naive B cells.

Monoclonal Antibodies

Generated by immunizing an animal, isolating B cells, fusing them with cancer cells to create immortalized hybridoma cells.
Hybridomas can be cloned to isolate clones secreting antibody of desired specificity.
Allows for producing unlimited amounts of antibody with a single defined specificity.
Technology developed by Koehler and Milstein in 1975.
Used in the clinic to treat disease.