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Antibodies: Friend & Foe

You’ve probably heard of “antibodies” before, but what are they, where do they come from, and why do they matter?

Antibodies are an essential part of the adaptive immune system, which means they can learn from past encounters with infections. The way they do this comes from how they they are made. To illustrate the process in a picture:

How antibodies are made. 1: B cells are generated with a unique B cell receptor. 2: Many different B cells are made with diverse B cell receptors. 3: When a B cell binds a pattern on an invading germ, it gets activated. 4 & 5: Activated B cells become long-lived memory cells or plasma cells that produce antibodies (secreted form of B cell receptor). 6: Those antibodies are ready to protect you when exposed to the same germ!

Antibodies are made from B cells. This is actually the most famous thing that B cells do, and sometimes people are surprised that my PhD studies were about OTHER functions of B cells — “wait, don’t B cells just make antibodies?”…you get it: underground and edgy, but I digress. When a new B cell is born in your bone marrow, it makes a B cell receptor by rearranging parts of the cell’s DNA (panel 1 in the picture above). This process has incredible amounts of diversity built-in, so the result is millions & millions of B cells have millions & millions of unique B cell receptors (panel 2) ready to detect the diverse invaders you will fend off every day.

When a germ tries to infect you, B cells that have receptors that bind patterns on the germ get activated and multiply, selecting for germ-binding (panel 3). These selected B cells can become long-lived memory cells, which guard for reinfection (panel 4), or differentiate into plasma cells that secrete large amounts of antibodies into the blood (panel 5). So you see, selecting B cells with a receptor that matches the germ results in making lots of antibodies which protect you (panel 6).

How do they protect you? There are two main categories: neutralization and non-neutralizing. Neutralization means the antibody blocks the infection by binding to the bug. Simple and effective! But the non-neutralizing types of protection are a lot more complicated, including activating other cells to kill or eat the bug, or starting up an immune cascade called “complement”, and more. The take-home message is antibodies target the invader, blocking it or alerting the immune system to attack.

Immune memory = a history of battles
As you encounter different infections throughout your life, the adaptive immune system makes a specialized response for each one, including production of antibodies that bind to the germ. In a way, this records a history of the germs you have encountered: we can find what infections a person has had by looking for antibodies that bind to the germ. For example, this can be useful in the clinic to test for HIV infection. A common test for HIV checks a person’s blood for antibodies against the virus.

Vaccines elicit protective antibodies
When you get a vaccine, the immune system reacts in a similar way to an infection: selecting B cells to make antibodies that bind to the proteins in the vaccine. Since those vaccine proteins are the same as the ones in the germ, when you are exposed to the germ the antibodies made against the vaccine protect you from infection.

1: Vaccines contain parts (subunit), broken (inactivated), or defective (attenuated) germs. 2: Antibodies are produced that bind to the proteins in the vaccine. 3: Infection by the live germ is blocked by these antibodies.

Autoantibodies can cause disease
Since the process of generating a B cell receptor is partially random, a large proportion of new B cell receptors actually bind to human proteins. To control this the immune system has processes of regulation called tolerance. The result of tolerance is the removal or suppression of the cells that target self. But when tolerance is compromised, antibodies that bind to self can be made, called autoantibodies. These autoantibodies can directly cause diseases like lupus, allergies, rheumatoid arthritis, thyroiditis, Sjögrens, and others. In fact, autoantibodies and autoreactive B cells may contribute to many more diseases in ways that we don’t yet understand, such as COPD/emphysema, type 1 diabetes, and MS.

In the clinic we have blood tests for autoantibodies. For some autoimmune diseases, a doctor will recommend B cell-depletion therapy (which, ironically, is made of an antibody that binds CD20 — a protein on B cells). This can treat diseases that are caused by B cells, but with a trade-off: the patient is temporarily unable to make new antibodies to fight infection.

B cells are helpful when they’re making antibodies in response to a vaccine or an invading microbe and protecting you from infection. But they can be harmful when tolerance fails in the case of autoimmunity. Like so much of the immune system, balance is the key to health.

Other articles by @sciencethomas:
Think HIV is Cured? Not Yet
The Flu Shot Can’t Give You the Flu
Fighting the Plague — A Story of HIV/AIDS

For more, follow me on Twitter @sciencethomas

Note: This and other things I write are my opinions about science and medicine, they should not be considered medical advice. If you have personal questions or concerns, talk with your doctor about these topics.

Supporting materials

B cell receptor signaling: http://f1000.com/prime/reports/b/5/40
Vaccine Immunology: http://www.who.int/immunization/documents/Elsevier_Vaccine_immunology.pdf
Autoantibodies in systemic autoimmune disease: https://www.jci.org/articles/view/78084
Autoantibodies in COPD & emphysema: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3919062/
Depletion of B cells can have positive clinical responses in early T1D (http://www.nejm.org/doi/full/10.1056/NEJMoa0904452)and in MS (http://www.nejm.org/doi/full/10.1056/NEJMoa1606468)