Microchimerism: I am a part of my daughter, and she is a part of me

| 25 Comments

Three years ago I became a chimera. Again. I am also geneticist. Surprisingly, the two are unrelated.

One of my current research projects involves studying the genetic component of the autoimmune disease Rheumatoid Arthritis. In this disease, the body’s immune system attacks its own tissues, usually around the joints, causing moderate to severe pain, and breakdown of the nearby bone. Rheumatoid Arthritis affects approximately 1% of the population. But, for reasons that we do not yet understand, the symptoms go away during pregnancy, in about 50% of women (in other patients the symptoms stay the same or worsen). While conducting background research for this project, I came across an amazing feature of human pregnancy: microchimerism.

What does microchimerism mean?

Let’s start with the biggest part of that word, chimera. In greek mythology, a chimera is a creature made of three different animals (a lion, a snake and a goat). In biology, the word chimera, or chimerism, can be used to refer to the existence of cells from genetically distinct individuals found in one person. So, microchimerism refers to the existence of a small set of cells of one genetic type intermixed with a large set of cells of another genetic type.

Let’s think about development for a minute.
My two year old shares about half of her DNA with her father, and about half with me. And, because we have raised her, she’s picking up our habits, good and bad. She smiles like her daddy, loves sharing snacks with our dog, and furrows her brow to glare at me when she’s upset (exactly like a million pictures of me growing up). I do everything I can to keep her a safe, while still allowing her the freedom to explore her world. It turns out that I’ve been doing this since she was a tiny, unrecognizable embryo.

Okay, you had a baby, but how did you become a chimera?
When I was pregnant, my body provided nourishment and protection. A portion of that protection came in the form of my immune system providing defense against infections. During pregnancy, some of my immune cells actually passed through the placenta, and became incorporated into my daughter’s developing body. This means that although most of the human cells in her body are her own (a unique combination of DNA from her father and from me), incredibly, there are some cells in her body that are actually mine. Even more extraordinary is that this sharing of immune cells is a two-way street. Some of the immune cells from her growing body passed back into mine. A subset of these cells became incorporated into my body, and will continue to replicate, sometimes for decades (Gammill and Nelson have a great review here, if you want to learn more).

Immune cells cross the plancetal boundary and
become incorporated among genetically dissimilar
cells where they continue to replicate


Whoa. So, you are both chimeras?
Yes. In fact, this exchange of cells occurs during all human pregnancies, with both male and female embryos. This means that some women have a small number of cells with male DNA from their sons, and men have some cells with female DNA from their mothers. So, we are all born as chimeras. Scientists are just now starting to understand how this exchange of cells affects our biology. My current interest in this topic is that fetal microchimerism might be responsible for some of the alleviation of symptoms during pregnancy for patients with Rheumatoid Arthritis.

It is also just mind-blowingly awesome.

It amazes me to realize that, right now, some of my daughter’s cells are incorporated into my body. There is, literally, a physical part of her with me wherever I go. And, similarly, a few of my cells are incorporated into her. The scientist in me is awestruck. But, as any parent will tell you, it doesn’t change how I feel. Regardless of our genetic relationship, I will always be a part of my daughter, and she will be a part of me.

25 Comments

Umm, check the spelling in the headline.

Also in this sentence: My current interest in this topic is that fetal michrochimerism…

Or as Mom would say, “That’s what you get for not calling.”

Glen Davidson

Thank you :) Clearly I need a copy-editor.

It is also just mind-blowingly awesome.

Hear, hear.

It the spelling thing UK English (Chimaera) vs US English (Chimera)?

So all males are really transsexuals. Hmmm… I like it.

rossum

You and your mother similarly share a small percentage / number of cells - right? Does that mean that your daughter shares a vanishingly small percentage / number of cells with her grandmother? How many generations can this sharing span?

I was just going to ask the same question!

@Paul Burnett,

No. You come from a single oocyte from you mother, that was set down quite early in embryo development. This will affect the somatic cells only, not get germline cells (as far as we know, so far).

Regardless of our genetic relationship, I will always be a part of my daughter, and she will be a part of me.

*sniff* This is the best blog post ever! [weeps uncontrollably]

So does this mean that if organisms are colonies of cells, that some of those cells are expatriots to their colony?

https://www.google.com/accounts/o8/[…]ArepslRs6TEc said:

@Paul Burnett,

No. You come from a single oocyte from you mother, that was set down quite early in embryo development. This will affect the somatic cells only, not get germline cells (as far as we know, so far).

I think that he was referring to the transfer from the mother during development. Since the transferred cells can persist for decades, more of her mother’s transferred cells could transfer to the baby if she was a teen mom than if she is over thirty. After a few decades most of the cells transferred from her mother would be gone and could not transfer to the next generation.

Why do you suppose symptoms of RA decrease (or increase) during pregnancy?

Ron Okimoto said:

https://www.google.com/accounts/o8/[…]ArepslRs6TEc said:

@Paul Burnett,

No. You come from a single oocyte from you mother, that was set down quite early in embryo development. This will affect the somatic cells only, not get germline cells (as far as we know, so far).

I think that he was referring to the transfer from the mother during development. Since the transferred cells can persist for decades, more of her mother’s transferred cells could transfer to the baby if she was a teen mom than if she is over thirty. After a few decades most of the cells transferred from her mother would be gone and could not transfer to the next generation.

Yeah, that seems sensible. In principle you could have cells from your grandmother. So if your mom had you when she was a teen, you could have three independent sets of haploid cells each with an independent set of 46 chromosomes.

Now the religious right says every living cell with 46 chromosomes is a human person– in fact more and more American states are passing laws mandating “personhood” laws. You could be three people and you could vote three times, but then I imagine the government would tax you three times.

diogeneslamp0 said:

*sniff* This is the best blog post ever! [weeps uncontrollably]

Pull yourself together! [*slap, slap*]

https://www.google.com/accounts/o8/[…]ArepslRs6TEc said:

@Paul Burnett,

No. You come from a single oocyte from you mother, that was set down quite early in embryo development. This will affect the somatic cells only, not get germline cells (as far as we know, so far).

In addition, the number of cells must be a very tiny percentage of the body’s cells. Cytogenetic testing is routinely performed on millions of men with neoplastic or congenital issues. Accidental discovery of populations of female cells is either unknown or exceptionally rare. These chimeric cells, if immune cells, would appear to effectively never give rise to malignant lymphoma, either (if someone has an example to the contrary I would be fascinated to learn of it), which, depending on what type of cells they are, might be weak evidence that there are very few of them or they don’t last very long. (Note that because transplantation therapies like bone marrow transplant are common, many lymphoma patients are chimeric due to therapy, and donor cells can give rise to malignancy; that’s well documented. But that’s different.)

Furthermore, some immune system cells are terminally differentiated and will die before dividing again, so some of these chimeric cells could die off.

Nevertheless, a cool topic. These seemingly subtle things may have powerful impact, especially on the immune system.

Mosaicism, in which a human body is composed of two or more clones with different genomes, rather than just cells with the same genome as the zygote, is not terribly rare. It’s usually noted only if one set of cells is abnormal, for example, mosaicism for trisomy 21.

SensuousCurmudgeon said:

diogeneslamp0 said:

*sniff* This is the best blog post ever! [weeps uncontrollably]

Pull yourself together! [*slap, slap*]

Thanks, he needed that.

Does this also mean your next offspring could have cells from your first (and so on)?

simonheffer1 said:

Does this also mean your next offspring could have cells from your first (and so on)?

OK, now it gets complicated.

Let’s see you’re a teen mom. You have cells in your body from your mom. You have your first baby. You get some of its cells, and it gets some of yours AND some of your Mom’s.

Now you have the cells of three people, yours, your Mom’s and your baby’s. Your baby has the cells of three people, itself, its mom and its grandmom.

Now you have your SECOND baby. You get some of its cells, and it gets some of yours AND some of your Mom’s AND some of your first kid’s.

Now you have the cells of FOUR people, yours, your Mom’s, and your first and second babies’. Your second baby has the cells of four people, itself, its mom, its grandmom and its sister.

Ah blblblblblblblbl.

diogeneslamp0 said:

Regardless of our genetic relationship, I will always be a part of my daughter, and she will be a part of me.

*sniff* This is the best blog post ever! [weeps uncontrollably]

Glad to bring people to tears. My work here is done.

Mark Sturtevant said:

Why do you suppose symptoms of RA decrease (or increase) during pregnancy?

At first people thought it might be hormones, but to my understanding no labs have been able to identify a hormone that varies with disease activity.

The anecdotal trend is that for the half-ish of mothers who do get better (remember that the other half stay the same or get worse!), symptoms increasingly diminish from the first to the second, then the second to the third trimester. Symptoms for these patients are generally low immediately following birth, but them sometime between 3mo-6mo postpartum they usually experience a flare of symptoms.

Perhaps the immune cells of the offspring provide some supplement to the immune cells of the mother? It is very difficult to say, but this might make sense if, in addition to the small set of immune stem cells that will become incorporated into the mother’s body, there are more “mortal” immune cells floating through the bloodstream. In this case, the father’s genotype could predict whether the mother will experience alleviation of symptoms.

It would be neat to see whether, with the same genetic father (assuming he’s homozygous for the putative disease-alleviating loci), women experience alleviation of symptoms during multiple pregnancies.

M. Wilson Sayres said: Perhaps the immune cells of the offspring provide some supplement to the immune cells of the mother? It is very difficult to say…

It had later occurred to me that there was the old idea that the mothers’ immune system becomes less reactive during pregnancy, as an adaptation for tolerating the foreign tissue of the embryo and fetus. That could neatly explain the decline in RA symptoms as it is an autoimmune disorder.

Lots of people mistook my mum for me on the phone and me for mum often asking is that Marilyn or her mum, so could this be an example of the “chimaera” effect. I wonder what determines what part of the body would be affected by chimaera.

Marilyn said:

Lots of people mistook my mum for me on the phone and me for mum often asking is that Marilyn or her mum, so could this be an example of the “chimaera” effect. I wonder what determines what part of the body would be affected by chimaera.

The resemblance is not likely due to chimerism, but mainly to genetics. The review article indicates, as I would have expected, that although these chimeric cells may have surprisingly strong effects on certain things, especially immune-related, they are few in number and seem to be mainly stem cells or immune cells. It is highly, highly unlikely that any actual tissue is made up of a very significant proportion of them. There is a study that claimed that some cervical epithelial cells in women might be chimeric cells, which is very interesting, but your tissues are mainly made up of your own cells, to put it mildly.

You inherited half of your genes from your mother. That is essentially true of anyone who survives to be an adult. Even men with XYY, or with Down’s Syndrome with two paternal chromosome 21’s, have almost half of their genes from their mother. Women with XXY or other “relatively extra X” syndromes would have a bit more. Essentially everybody else who has a normal enough genome to survive to adulthood has almost exactly half their genes from each parent.

The degree to which people look like their mother depends on which genes they got from her, and environmental factors.

Mark Sturtevant said:

It had later occurred to me that there was the old idea that the mothers’ immune system becomes less reactive during pregnancy, as an adaptation for tolerating the foreign tissue of the embryo and fetus. That could neatly explain the decline in RA symptoms as it is an autoimmune disorder.

If it did neatly describe it, that would be wonderful. But, RA symptoms only get better in about half of patients (while in the other half the symptoms stay the same, and in some they get worse!). It is certainly possible that this is a contributing factor, but I imagine that it (less reactive immune system during pregnancy) would be more global across pregnancies. I was also talking with someone recently that the globally less reactive immune system might not be completely accurate. For example:

Inflammation and pregnancy: http://www.ncbi.nlm.nih.gov/pubmed/21401634

The immune system during pregnancy: http://www.ncbi.nlm.nih.gov/pubmed/21488887

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This page contains a single entry by M. Wilson Sayres published on May 29, 2013 8:13 AM.

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