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The major players of humoral immunity are B-cells. They develop in the bone marrow and complete their maturation in the spleen. Similar to T-cells, B-cells are formed in billions of variations, each carrying a unique surface protein, called B-cell receptor, BCR. Just like T-cells, they also learn to not react to the body’s own antigens; those that react to self-molecules are eliminated or ignored. The majority of mature B-cells, namely the follicular B-cells, circulate to secondary lymphoid organs – the same locations as mature T-cells, where they expect encounters with pathogens. T-cells and B-cells are usually separated into defined T-cell and B-cell zones within these organs.
Here again, specific immunity relies on the invading pathogen finding a match among these many variations of B-cells. Only cells that can bind to the pathogen, can be activated to produce antibodies. B-cell surface receptors, BCRs, are actually membrane-bound antibodies. The existence of BCR variations means that the body already has all the antibodies it can possible make right from the start. For resource management purposes, it makes sense not to produce all of them in large quantities. Instead, presence of an invading pathogen selectively activates the binding B-cell, which then multiplies and produces huge amounts of that particular antibody to combat the pathogen.
An antibody is basically a protein whose structure consists of variable and constant regions. The variable regions give the antibody its uniqueness, much like the bit, or blade, of a key. This is where it binds to a specific antigen, which is the lock.
There are several classes of antibodies, differing in their constant regions. Different antibody classes engage different mechanisms to neutralize the antigen. The surface receptors on B-cells are IgM and IgD molecules.
Each B-cell has thousands of identical copies of BCR on its surface. When a pathogen binds, it usually binds to several of these receptors, linking them together, triggering endocytosis of the pathogen. B-cells then cut the pathogen into pieces and display them on MHC-II molecules on their surface. Thus, B-cells now become antigen-presenting cells, but are not yet activated. In most cases, activation of antigen-primed B-cells does not happen until they are stimulated by antigen-specific T-helper cells.
Nearby, in the T-cell zone, T-helper cells are activated by dendritic cells carrying antigens of the same pathogen, and become effector T-helper cells. Some of these effector cells leave lymph nodes for the site of infection, while other, namely the follicular helper cells, migrate to T-cell B-cell borders, and bind to the antigens presented by B-cells. This interaction triggers T-cells to produce helper factors, which activate B-cells.
Activated B-cells undergo first rounds of proliferation and differentiation, giving rise to the first batch of plasma cells producing antibodies, mainly of IgM class; and a group of cells that are committed to become memory B-cells. The latter undergo antibody class switching; and form a so-called germinal center, where they go through cycles of multiplication and hypermutation in the immunoglobulin gene. This process produces slightly different variations of the same antibody, which are then subject to a binding test to the same antigen. Those that no longer bind are discarded, while the remaining compete for binding to antigen-specific T-helper cells. B-cells with the highest affinity to the antigen win the interaction with T-helpers and exit the germinal center. They can either become long-lived memory B-cells, or differentiate into antibody-producing plasma cells. This second batch of plasma cells produces better antibodies and lives longer than the first batch. They also make antibodies of different classes (predominantly IgG), which neutralize the pathogen in many different ways.
Upon reexposure to the same pathogen, memory B-cells mount a much faster immune response. Plasma cells form within hours, producing huge amounts of the best possible antibody within days, destroying the pathogen so quickly that no signs of illness are noticeable.
