Adaptive Immunity: B Cells and Antibody Production

Adaptive immunity is the body’s specific, slower defense that recognizes particular antigens, and in humoral immunity B lymphocytes (B cells) produce antibodies that bind to an antigen and mark it for destruction. In brief: an antigen is a molecule, usually on a pathogen, that triggers an immune response. Each B cell recognizes one antigen. When it meets its antigen and receives help, it divides and produces plasma cells that release antibodies, and memory cells that make the response faster and stronger the second time.

Adaptive immunity gives long-lasting protection, and it is the basis of vaccination. This guide explains antigens and antibodies, the steps of the B cell response, the difference between the primary and secondary response, how immunological memory works, works through an antibody-level example and corrects common mistakes.

What is adaptive immunity?

Adaptive (acquired) immunity develops during life as a result of exposure to antigens. Its main features are:

• Specificity: each lymphocyte responds to a particular antigen.
• Diversity: the body can recognize millions of different antigens. Random rearrangement of gene segments in developing lymphocytes generates a huge variety of receptors, estimated at more than 10⁹ different ones.
• Memory: after the first exposure, memory cells provide a faster and stronger response on later exposures.
• Self-tolerance: lymphocytes that react against the body’s own molecules are mostly eliminated or inactivated while they develop.

There are two arms. Humoral immunity works through antibodies in body fluids and is carried out by B cells. Cell-mediated immunity works through T cells that attack infected cells directly, and is covered in the next article.

What are antigens?

An antigen is any molecule that the immune system recognizes as foreign and that triggers a response. Most are proteins or polysaccharides on the surface of pathogens such as bacteria, viruses, fungi and parasites, or toxins. They can also be on transplanted tissue, pollen or the surface of cancer cells. The small part of an antigen that the antibody or receptor binds to is the epitope. A pathogen has many different antigens and can therefore stimulate many different B cells.

What are antibodies?

Antibodies (immunoglobulins, Ig) are Y-shaped proteins made of four polypeptide chains: two identical heavy chains and two identical light chains, held by disulfide bonds. Each arm of the Y has a variable region, whose amino acid sequence differs between antibodies and forms the antigen-binding site, which fits one specific antigen like a lock and key. The stem is the constant region, which is the same in each class and allows binding to phagocytes and to complement.

Antibodies help in the following ways:

• Neutralization: they bind to toxins or to the viral proteins used to enter cells, which blocks them.
• Agglutination: they clump pathogens together, so phagocytes can engulf them more easily.
• Opsonization: they coat the pathogen and act as a signal for phagocytes.
• Activation of complement: they trigger proteins that damage the pathogen’s membrane.

Five classes exist: IgG (most common in blood, crosses the placenta), IgM (the first made in an infection), IgA (in secretions such as saliva, tears and milk), IgE (in allergies and defense against parasites) and IgD.

How do B cells make antibodies?

B cells develop in the bone marrow. Each B cell has thousands of copies of one type of antibody on its surface as a receptor. The process of clonal selection is:

1. Recognition: a B cell with a receptor that fits the antigen binds it. This happens mainly in lymph nodes and the spleen.
2. Activation: the B cell takes in the antigen and shows a part of it on its surface. A helper T cell that recognizes the same antigen binds to it and releases chemical signals (cytokines). Most B cell responses need this help.
3. Clonal expansion: the B cell divides repeatedly by mitosis and produces a clone of identical cells, all specific for the same antigen.
4. Differentiation: most of the clone becomes plasma cells, which are antibody factories. A plasma cell can release thousands of antibody molecules per second. A few become memory B cells, which stay in the body for years or decades.

The antibodies are released into the blood and lymph and reach the infection site. As the pathogen is eliminated, the response declines, and most plasma cells die.

What are the primary and secondary responses?

The first time that a person meets an antigen, the primary response is slow. There are few B cells specific for the antigen, so it takes several days (usually 5 to 10) before antibodies are detectable, and the level is modest. Symptoms of the disease may appear before the immune response is effective.

If the same antigen enters again, memory B cells respond right away. The secondary response is faster (1 to 3 days), larger (antibody levels are often 10 to 100 times higher) and lasts longer, and the antibodies bind more strongly to the antigen. The pathogen is usually eliminated before it causes symptoms, so the person is immune. Vaccines use this principle.

Primary and secondary immune responses compared

Worked example: reading an antibody-level graph

A person receives a vaccine on day 0 and a booster on day 28. The concentration of specific antibody in the blood is measured. Values are in arbitrary units per milliliter.

1. Primary response: there was no antibody on day 0, and a small amount (2) appeared by day 7. A peak of 10 was reached around day 14, then the level fell to 6 by day 28.
2. Secondary response: after the booster on day 28, the level rose within 7 days to 120, which is 120 ÷ 10 = 12 times the primary peak. By day 42 it was 200, which is 20 times the primary peak.
3. Interpretation: the faster and larger rise after the second dose shows that memory B cells were produced in the first response and reacted quickly. The booster explains why many vaccines require more than one dose.
4. Speed: one week after the first dose, the level had reached only 20 percent of the primary peak (2 ÷ 10). One week after the booster, it had already reached 60 percent of the secondary peak (120 ÷ 200), so the response was much faster.

The drop from 10 to 6 between days 14 and 28 shows that antibodies do not last forever. They are broken down, and the protection after vaccination depends on memory cells, which can produce new antibodies when needed. The data are invented for illustration.

How was antibody immunity discovered?

In 1890, Emil von Behring and Shibasaburo Kitasato showed that serum from animals immunized against diphtheria or tetanus could protect other animals. The antitoxin was the first serum therapy, and von Behring received the first Nobel Prize in Physiology or Medicine in 1901. Paul Ehrlich proposed in the 1890s that cells have receptors that bind antigens. Macfarlane Burnet formulated the clonal selection theory in 1957. Rodney Porter and Gerald Edelman worked out the structure of antibodies in the 1960s, and they shared the 1972 Nobel Prize in Physiology or Medicine. Georges Köhler and César Milstein developed monoclonal antibodies in 1975, which are used in diagnostics and in treatments for cancer and autoimmune diseases.

Which mistakes are common?

Mistake 1: Saying that the body makes a new antibody for each antigen from scratch

B cells with matching receptors already exist in small numbers. The antigen selects and multiplies them (clonal selection).

Mistake 2: Confusing antigen and antibody

The antigen is the foreign molecule. The antibody is the protein made by the body that binds to it.

Mistake 3: Thinking that plasma cells and memory cells have the same function

Plasma cells make antibodies now. Memory cells remain for rapid response later.

Mistake 4: Saying that antibodies kill pathogens directly

Antibodies mostly neutralize or tag them. Phagocytes and complement do the killing.