Antibodies (immunoglobulins) for dummies

Wait, what do antibodies have to do with blood cancer? A lot as it turns out. Many blood cancers are of a type of lymphocyte called a b-cell. The primary function of b-cells is to create antibodies. Blood cancer interferes with that function. There is great deal more to know on about antibodies, but to really understand them we have to go back and do a review of basic cell biology.

Cells are the building blocks of life. Inside the nucleus of every cell are chromosomes, DNA and genes that tell every cell what to do. Skin cells get different instructions than brain cells and muscle cells. Cancer is a disease that starts at the cellular level. Brain cancer is a result of a brain cell gone bad and multiplying uncontrollably. Blood Cancer is blood cells gone bad.

But its only one type of blood cell that goes bad. With Blood Cancer it is often a lymphocyte. A lymphocyte is a type of white blood cell. A b-cell is a type of lymphocyte and critical to our immune system because b-cells generate antibodies.

A b-cell receptor is a type of Y shaped antibody which is a protein that is on the surface of a b-cell. The stalk of the Y is embedded in the cell and instead of two arms, it has four. The inner arms of the Y are called the heavy chain arms and the outer arm light chains. The name “antibody” comes from the German word “antikorper”, as named by the German scientist, Paul Ehrlich, in 1891. Antitoxin might have been a better name.

Antibodies are also called immunoglobulins. Immuno means pertaining to the immune system. Globulin comes from globule meaning a small round particle. But wait, antibodies are Y shaped not round, what the heck? As it turns out, the molecules that make up antibodies are round shaped, hence the name immunoglobulins. Where else have you heard about immunoglobulins from? IGHV mutation testing that is the most important prognostic marker for CLL is done on an immunoglobulin heavy chain. And IVIG treatments you hear about some taking are just immunoglobulin (antibody) infusions. More on these later. First lets discuss how antibodies work.

There can be thousands of b-cells in a single drop of blood. Healthy b-cells live for a couple of weeks and patrol the body looking for antigens. I think everyone knows an antigen has something to do with a virus or bacteria. But did you ever think of what the name literally means? An anti-gen is an antibody generator. If you have the covid virus in your blood, god forbid, it has an antigen molecule on its surface which is like a lock only one key can open.

That key is the b-cell receptor (BCR) Y shaped antibody and exists on just the right b-cell. The Y arms of the BCR have a variable shape at the tip that forms a key that binds to a particular antigen. A b-cell with a bcr that binds to a measles antigen will not bind to a covid antigen. Now to the really cool part.

Lets say your B-cell with the right key found a covid antigen and binds to it. Right after that happens a T-cell comes trucking along, takes notice, and activates your b-cell. Your b-cell swallows up the antigen and goes through a stage called differentiation where it evolves into plasma cells and into memory b-cells. The plasma cells make bunches of little Y shaped antibodies with the exact key to fit the covid antigen. These little Y’s go swimming through your blood looking for covid antigens and wipe them out in a variety of very cool ways. The antibodies can neutralize the virus by occupying all its receptors. My favorite process is where the antibodies tag the virus so other virus killers will come along, recognize it come and eat it. Too cool.

So what does that have to do with blood cancer? Well our blood cancer has a queen bee, a dysfunctional mother cell who divided into millions of b-cells that do not work right. Blood Cancer cells do not die as they are supposed too and crowd out all our good cells. How poorly our blood cancer cells work might be a function of when they went bad in their life cycle. That leads us back to IGHV mutation testing.

Many on here know that their CLL prognosis is generally better with mutated IGHV. But did you have any real idea what IGHV meant? IG is for immunoglobulin (antibody). HV is for the heavy chain variable region where the antibody is mutated. Thats the region where tips of the four arms of the Y are. Why is it variable? That is because that is where the key to bind to antigen locks are made, so the tip of the antibody varies from one b-cell to the next.

B-cells go through a maturing process. The b-cell receptor, a Y shaped antibody on the cell surface, matures as well as the key at the tip of the end of the Y arms are shaped (mutated) to fit an antigen. If a queen bee b-cell goes bad before the tips mutated, she is unmutated, as will be her billions of cell cell children. If her tips went through some mutation, then all of her kids will be mutated. Scientists can take a cll cell, look at the b-cell receptor at the tip of the Y (variable heavy chain) and see if it is mutated. All of those cll cells, mutated or not, will be of no help if a flu or covid virus comes along. The “key” on the cll receptor will not fit the flu or covid antigen. Another analogy instead of lock and key might be to think of antigens and antibodies as pieces of a jigsaw puzzle. The tip of the antibody that binds to the antigen has to be perfectly shaped to fit the antigen.

And now you know what people are talking about on here if they write about IVIG infusions. For some of us with CLL, as our CLL cells take over we lose the functional cells that make antibodies we need to fight viruses and bacteria. IVIG is an acronym for intravenous immunoglobulins, another way of saying intravenous antibodies. If our bodies get to the point they do not make enough antibodies, we can get our antibodies from blood donors. Its not ideal, but it works and IVIG infusions allow for a lot of folks to used borrowed antibodies to keep them from getting sick, actually quite amazing when you think about it.

Memory b-cells are pretty cool too. Remember that after a b-cell gets activated through its bcr, it goes through a process that creates plasma cells (that secrete antibodies) and memory cells? The memory cells hang out and “remember” the antigen so if it comes back the whole system doesn’t have to reboot. Memory cells can live for decades. I am guessing I still have some that remember my smallpox vaccines.

Well I hope I have not thoroughly confused you. And I should add that this explanation might not be 100% accurate partly because of liberties taken to dumb it down and partly because the topic is mostly over my head and I could easily have confused some terms. I have to admit, I find it fascinating how it all works.

Maybe next time we can talk about monoclonal antibody treatments that have revolutionized cll treatments and other illnesses as well. It is good to live in a time where scientists know how viruses like covid work on a cellular level. They will figure it out eventually. And now you understand better why they want to collect blood from people who have survived covid and mine the antibodies from their blood.