Adaptive Immunity: Specific Defenses of the Host |
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Each B-cell has unique antigen receptors on its surface and responds to one specific antigen (hypothetically).
B-cells are produced by stem cells in the bone marrow (like T-cells) remain in the bone marrow to mature.
After maturation, B-cells leave the thymus and move to lymphoid tissues, where they are most likely to encounter pathogens that are more susceptible to the cellular immune system.
B-cells that don't recognize host tissue as "self" and are potentially harmfully reactive are eliminated during maturation by undergoing apoptosis, a process called clonal deletion.
Top: a B-cell undergoing apoptosis
Bottom: a normal, healthy B-cell.
B-cells are activated when antigen binds to receptors on the B-cell surface, followed by a co-stimulatory signal, usually provided by a helper T-cell. Antigens that require co-stimulation by a T-cell to activate a B-cell are T-dependent antigens and are usually proteins.
In order for the helper T-cell to stimulate the B-cell both must be activated - this usually requires that the B-cell internalize the antigen, process it, and then present it on the cell surface bound to a class II HLA molecule. The HLA-antigen complex is recognized by a receptor on the surface of the T-cell (the T-cell receptor, or TCR).
The B-cell expresses an activation receptor on its surface (CD40) that binds to a complementary ligand (CD154) on the surface of the helper T-cell. This interaction will co-stimulate the B-cell, activating it to clonally proliferate. In addition, the helper T-cell will secrete interleukins that will promote growth and antibody production by the activated B-cell.
The helper T-cell would normally have been activated by interaction with a macrophage or dendritic cell but the B-cell can act as an antigen presenting cell as well. The B-cell can express B7 proteins on its surface which will bind to CD28 on the surface of the helper T-cell. The combination of TCR-HLA/antigen binding and B7-CD28 binding will activate the T-cell.
The activated B-cell clonally proliferates to produce a population of plasma cells and memory cells, which all recognize the same antigen. This process is called clonal selection.
B cells also have TLRs. When a PAMP such as LPS binds the TLR, it enhances the response of the B cell to the antigen.
Pathogens coated with fragments of the complement protein C3 are not only opsonized for phagocytosis but also bind more strongly to B cells that have bound the pathogen through their BCR. This synergistic effect enables antibody production to occur at doses of antigen far lower than would otherwise be needed.
Antigens that stimulate B-cells directly, without co-stimulation by helper T-cells, are T-independent antigens. T-independent antigens are usually polysaccharides or lipopolysaccharides (like those found in bacterial capsules).
T-independent antigens cross link antigen receptors on the surface of B-cells to activate them but don't generate as strong a response (no memory cells, IgM is the only antibody class produced, and the immunity doesn't last long).
The population of B-cells in an individual's body may be able to respond to as many as 1015 different antigens. (How in the world could you code for that many different antigen receptors? We don't have but about 20,000 - 25,000 genes to begin with - so how does this work? You bet I've got another page for you, click here)
