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Tags: Health, Biotechnology, Culture, Medicine, Science

B Cells — giveth and taketh away

One of the main functions of B cells, we already said, is to produce the antibodies we use to fight infections.

Antibodies are just part of one arm of a very complex two-part immune system that mammals and vertebrates have. The first is an ancient innate immune system which is the dominant system found in plants, fungi, insects, and other more primitive organisms. But we also have a second and more recent adaptive immune system, which is one of the crowning achievements of vertebrate evolution, along with the brain’s cortex, and other innovations.

The primary goal of the adaptive immune system is to create a memory of an infection by a pathogen, but especially new pathogens. This is important since infectious agents are always evolving, often very rapidly.

Antibodies are part of the adaptive immune system. And B cells genetically encode, produce and secrete antibodies, proteins also known as immunoglobulins.

The genetic key to our adaptive immune system’s ability to… adapt… comes from two genetic processes with typically cryptic scientific names:

Somatic hypermutation

V(D)J recombination

Let’s take each in turn to see how a part of our adaptive immune cells, the B cells, work.

Somatic hypermutation is a million-fold increase in mutations in a small portion of the antibody’s gene, the part which codes for the antibody’s ability to recognize and bind to a particular part of the invading organism.

Imagine we have a B cell which produces an antibody against the COVID-19 virus SARS-CoV-2. If that B cell recognizes another SARS-CoV-2 virus, the B cell begins to divide and make many more B cells. Each of those daughter B cells undergoes somatic hypermutation within the antibody gene making many small variations. The goal is to produce antibodies that more effectively bind to that antigen, the materials that make up the virus.

V(D)J recombination occurs in developing B and T cells and is another process for randomizing antibody genes. An antibody gene has multiple blocks of DNA called variable (V), diversity (D) and joining (J) regions, and these specific regions undergo an almost random series of combinations and deletions, producing a tremendous diversity of antibodies able to bind to any antigen produced by bacteria, viruses, parasites and worms.

Simplistic overview of V(D)J recombination (Wikimedia Commons)

Both of these very novel genetic processes create huge diversity within a single organism, and is essential to build an adaptive immune system capable of recognizing almost any invasive and harmful pathogen.

These are very important exceptions to the popular trope that all our cells are genetically identical.

There are several ways in which that idea is not actually true. First, each cell is subject to all kinds of genetic damage, both internal and external. External factors include solar radiation, environmental chemicals, etc. Internal factors include the production of oxidizing free radicals from normal cellular processes such as respiration. Although we have numerous and effective DNA repair systems in place which address most of those genetic assaults, some damage and change persists in many of our cells. Most of those changes have no effect. Some do, and some of those lead to diseases.

The somatic hypermutation and V(D)J recombination are hyperactive mutations which our evolution has captured and harnessed for the purposes of immune adaptability.

This is a tremendous evolutionary gift, turning mutations into a feature and benefit.

However, there is no free lunch. The processes of hypermutation and recombination which gives us our adaptive immune system, can also occasionally go wrong. When that happens, the same processes are also implicated in sometimes creating lymphomas.