B Cells and Adaptive Immune Response

Study Notes

B cells are key components of the adaptive immune response.
They play critical roles in antibody production and antigen presentation.
B cells are central to the clonal selection theory.
Clonal selection theory proposes antigen-specific B cells are activated and expanded upon encountering their cognate antigen.
This theory is fundamental to understanding how the immune system responds to diverse pathogens.
Antibody diversity is generated through processes including somatic hypermutation.
This ensures a broad repertoire of antibodies capable of recognizing various antigens.

The adaptive response begins approximately 96 hours after initial infection.
It is activated if the innate immune system fails to control the infection.
B and T lymphocytes are the key players in the adaptive response.
B cells mediate the adaptive humoral immune response.
B cells produce antibodies (plasma cells).
T cells mediate the adaptive cell-mediated immune response.
T cells include Tc, Th1, Th2, TEH, and Th17 cells.
Activation of the adaptive immune response occurs in secondary lymphoid tissue (e.g., lymph nodes, spleen, MALT).

Each lymphocyte has a unique receptor with specific characteristics.
Foreign antigen interaction with the lymphocyte receptor leads to lymphocyte activation.
Activated lymphocytes proliferate (increase in number) and differentiate into effector cells.
These effector cells have identical antigen receptors to the original parent cell.
Lymphocytes with self-molecule receptors are deleted early in development, ensuring they are absent from mature lymphocytes.

Each B cell produces an antibody with unique specificity.
The collection of antibody specificities is called the antibody repertoire.
Humans possess approximately 10^11 antibody specificities.
Encoding each specificity via separate genes is inefficient.
Antibody diversity arises from somatic gene recombination and somatic hypermutation.

DNA encoding antibody variable and constant regions is separated in all cells except B cells.
During B cell development, coding segments are brought together to create functional antibody molecules.
This occurs for both heavy and light chains.
Light chain genes, like kappa (κ) and lambda (λ), exist.
Kappa light chain genes are located on chromosome 2.
Lambda light chain genes are on chromosome 22.
The light chain V region is derived from combining V (variable) and J (joining) gene segments.
The V gene segment encodes the first amino acids (95-101).
The J gene segment codes for the rest of the domain (~13 residues).
V region DNA is separated from the C region DNA by non-coding sequences removed through RNA splicing.
For kappa light chains, approximately 38 V segments and 5 J segments exist.
For lambda light chains, roughly 30 V segments and 4 J segments are observed.
A variety of V regions potentially are produced (e.g., 190 for kappa and 120 for lambda).
Heavy chain genes comprise V, D (diversity), and J gene segments.
This results in about 5,520 likely V regions and ~1.7 x 10^6 different antibody specificities from combining H and L chains.

Imprecise joining of segments: Nucleotide additions or deletions during segment joining lead to variability.
Non-functional rearrangements are eliminated.
Somatic hypermutation: Point mutations in V regions of rearranged H and L chain genes occur in secondary lymphoid organs.
High-affinity antibodies are generated during an immune response.

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