“Silenced” B Cells Loudly Proclaim the Case for a Creator

silencedbcells

BY FAZALE RANA – AUGUST 1, 2018

When I was an undergraduate student studying chemistry and biology, I hated the course work I did in immunology. The immune system is fascinating, to be certain. And, as a student, I marveled at how our body defends itself from invading microorganisms. But, I hated trying to keep track of the bewildering number of the cells that comprise the immune system.

But my efforts to learn about these cells has finally paid off. It allows me to appreciate the recently discovered insights into the role “silenced” B cells play in the immune system. Not only do these insights have important biomedical implications, but, in my view, they also add to the mounting evidence for creation and further validate a creation model approach to biology.

First discovered thirty years ago, these cells were initially deemed nonfunctional junk produced by a flawed immune system. And this view has persisted for three decades.Immunologists viewed silenced B cells as harmful. Presumably, these cells impair immune system function by cluttering up immune tissues. Or worse, they considered these cells to be potentially deadly, contributing to autoimmune disorders. Yet, immunologists are changing their view of’silenced B cells, thanks to the efforts of researchers from Australia.1

A Brief (and Incomplete) Primer on Immunology

To understand the newly discovered role silenced B cells play in the immune system, a brief primer on immunology is in order.

It goes without saying that the immune system’s job is to protect the body from pathogens. To do this, it must recognize pathogens as foreign materials. To put it another way, it must distinguish self from nonself. (Autoimmune disorders result when the immune system mistakes the body’s own tissues as foreign materials, and then attacks itself.)

An incredibly complex biological system, the immune system contains one component called the humoral immune system. This part of the immune system relies on proteins, such as antibodies, circulating in extracellular fluids to mediate the body’s immune response.

Plasma cells secrete antibodies into the circulatory system. Antibodies then bind to the invading pathogen, decorating its surface. The antibodies serve as a beacon that attracts certain immune cells, such as macrophages and killer cells, that will engulf the pathogen, clearing it from the body.

Plasma cells originate in bone marrow as B cells (also known as B lymphocytes). B cells develop from hematopoietic stem cells. As they develop, genes in the developing B cell genome that encode for antibodies (and receptor proteins) undergo rearrangements (just like shuffling a deck of cards). These rearrangements generate genes that encode an ensemble of receptor proteins that reside on the B cell surface, with each receptor protein (and corresponding antibody) recognizing and binding a specific pathogen. Collectively, these cell surface receptors (and antibodies) can detect a large and varied number of foreign agents.

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Image credit: Shutterstock

After developing in the bone marrow, B cells migrate to either the spleen or lymph nodes. Here, the B cells are exposed to the flow of lymph, the fluid that moves through the lymphatic circulatory system. If pathogens have invaded the body, they will encounter B cells in lymph tissue. If a B cell has a receptor that recognizes that particular pathogen, it will bind it. This binding event will trigger the transformation of the B cell. Once activated by the binding event, the B cell migrates into a region of the lymph tissue called the germinal center. Here the B cells undergo clonal expansion, rapidly proliferating into plasma cells and memory B cells. The plasma cells produce antibodies that help identify the pathogen as a foreign invader. The memory B cells hang around in the immune tissue so the immune system can rapidly respond to that pathogen if it invades the body in the future.

A Flaw in the Immune System?

During the B cell maturation process in the bone marrow, about 50 percent of the nascent B cells produce cell surface receptors that bind to materials in the body, instead of pathogens. That is, these B cells can’t discriminate self from nonself. This outcome is a by-product of the random-shuffling mechanism that generates protein receptor diversity. The random shuffling of the genes is equally likely to produce receptors that bind to materials in the body as it is pathogens. But when this misidentification happens, an elaborate quality control system kicks in, either eliminating the faulty B cells or reworking them so that they can be a functioning part of the immune system. This reworking process involves additional gene shuffling with the hope of generating cell receptors that recognize foreign materials.

However, a few of the faulty B cells escape destruction and avoid having their genes reshuffled. In this case, the immune system silences these cells (called anergic cells), but they still hang around in immune tissue, clogging things up. It seemingly gets worse: if these cells become activated they can cause an autoimmune reaction—just the type of sloppy design evolutionary mechanisms would produce. Or is it?

A Critical Role for Silenced B Cells

Recent work by the research team from Australia provides a rationale for the persistence of silenced anergic B cells in the immune system. These cells play a role in combating pathogens such as HIV and campylobacter, which cloak themselves from the immune system by masquerading as part of our body. While these pathogens escape detection by most of the components of our immune system, they can be detected by silenced B cells with receptors that recognize self as nonself.

The silenced B cells are redeemed by the immune system in the germinal center through a process called receptor revision. Here the genes that encode the receptors experience hypermutation, altering their receptors to the extent that they now can recognize foreign materials. But the capacity of the receptors to recognize self serves the immune system well when infectious agents such as HIV or campylobacter invade.

The researchers who made the discovery think that this insight might one day help pathologists do a better job treating autoimmune disorders. They also hope it might lead to a vaccine for HIV.

A Remarkable Turnaround

In a piece for Science Alert, journalist Peter Dockrill summarizes the significance of the discovery: “It’s a remarkable turnaround for a class of immune cells long mistaken for dangerous junk—and one which shows there’s still so much we have to learn about what the immune system can do for us, and how its less than perfectly obvious mechanisms might be leveraged to do us good.”2

The surprise expressed by Dockrill reflects the influence of the evolutionary paradigm and the view that biological systems must be imperfect because of the nature of evolutionary mechanisms. And yet this discovery (along with others discussed in the articles listed in the Resources section) raises questions for me about the validity of the evolutionary paradigm. And it raises questions about the usefulness of this paradigm, as well. Viewing silenced B cell as the flawed outcome of evolutionary processes has stood in the way of discovering their functional importance, delaying work that “might be leveraged to do us good.”

The more we learn about biological systems, the more evident it becomes: Instead of being flawed, biological designs display an ingenuity and a deep rationale for the way they are—as would be expected if they were the handiwork of a Creator.

Resources

Endnotes

  1. Deborah L. Burnett et al., “Germinal Center Antibody Maturation Trajectories Are Determined by Rapid Self/Foreign Discrimination,” Science 360 (April 13, 2018): 223–26, doi: 10.1126/science.aa03859; Ervin E. Kara and Michel C.Nussenzweig, “Redemption for Self-Reactive Antibodies,” Science 360 (April 13, 2018): 152–53, doi:10.1126/science.aat5758.
  2. Peter Dockrill, “Immune Cells We Thought Were ‘Useless’ Are Actually a Weapon Against Infections Like HIV,” Science Alert (April 16, 2018), https://www.sciencealert.com/new-discovery-bad-immune-cells-actually-secret-weapon-against-infection-b-silenced-redemption-lymphocytes.
Reprinted with permission by the author
Original article at:
https://www.reasons.org/explore/blogs/the-cells-design/read/the-cells-design/2018/08/01/silenced-b-cells-loudly-proclaim-the-case-for-a-creator

Love Is in the Air and It Smells Like Intelligent Design

loveisintheair

BY FAZALE RANA – FEBRUARY 14, 2018

Being the hopeless romantic, I worked hard last year to come up with just the right thing to say to my wife on Valentine’s Day. I decided to let my lovely bride know that I really liked her signaling traits. Sadly, that didn’t go over so well.

This year, I think I am going to tell my wife that I like the way she smells.

I don’t know how Amy will receive my romantic overture, but I do know that scientific research explains the preference I have for my wife’s odors—it reflects the composition of a key component of her immune system, specifically her major histocompatibility complex. And, my wife’s immune system really turns me on.

Odor Preference and Immune System Composition

Why am I so attracted to my wife’s scents, and hence, the composition of her immune system? Several studies help explain the connection.

In a highly cited study, researchers had men sleep in the same T-shirt for several nights in a row. Then, they asked women to rank the T-shirts according to odor preference. As it turns out, women had the greatest preference for the odor of T-shirts worn by men who had MHC genes that were the most dissimilar to theirs.

In another oft-cited study, researchers had 121 men and women rank the pleasantness of T-shirt odors and found that the ones they most preferred displayed odors that were most similar to those of their partners. Based on the results of another related study, it appears that this odor preference reflects dissimilarities in immune systems. Researchers discovered that the genetic differences in the MHC genes for 90 married couples were far more extensive than for 152 couples made up by randomly combining partners.

Body Odor and the Immune System

So, how does odor reflect the composition of the MHC genes? Researchers believe that the breakdown products from the MHC during the normal turnover of cellular components serves as the connection between the immune system and body odors.

The MHC is a protein complex that resides on the cell surface. This protein complex binds proteins derived from pathogens after these organisms have infected the host cell and, in turn, displays them on the cell surface for recognition by the cells of the immune system.

 

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Association of Pathogen Proteins with MHCs

Image credit: By Scray (Own work) [CC BY-SA 3.0 (https://creativecommons.org.licenses/by-sa/3.0)], via Wikimedia Commons

Organisms possess a large number of MHC variants, making the genes that code the MHCs some of the most diverse in the human genome. Because the MHCs bind proteins derived from pathogens, the greater the diversity of MHC genes, the greater the capacity to respond to infectious agents.

As part of the normal turnover of cellular components, the MHCs are constantly being broken down and replaced. When this happens, protein fragments from the MHCs become dispersed throughout the body, winding up in the blood, saliva, and urine. Some researchers think that the microbes in the mouth and on the skin surface lining body cavities metabolize the MHC breakdown products leading to the production of odorants. And these odors tell us something about the immune system of our potential partners.

Advantages of Having a Partner with Dissimilar MHC Genes

When men and women with dissimilar MHC genes pair up, it provides a significant advantage to their children. Why? Because parental MHC gene dissimilarity translates into the maximal genetic diversity for the MHC genes of their children. And, as already noted, the more diverse the MHC genes, the greater the resistance to pathogens and parasites.

The attraction between mates with dissimilar immune genes is not limited to human beings. This phenomenon has been observed throughout the animal kingdom. And from studying mate attraction of animals, we can come to appreciate the importance of MHC gene diversity. For example, one study demonstrated that salmon raised in hatcheries displayed a much more limited genetic diversity for their MHC genes than salmon that live in the wild. As it turns out, hatchery-raised salmon are four times more likely to be infected with pathogens than those found in the wild.

Is Love Nothing More than Biochemistry?

Does the role odor preference plays in mate selection mean that love is merely an outworking of physiological mechanisms? Does it mean that there is not a spiritual dimension to the love we feel toward our partners? Does it mean that human beings are merely physical creatures? If so, does this type of discovery undermine the biblical view of humanity?

Hardly. In fact, this discovery makes perfect sense within a Christian worldview.

In his book The Biology of Sin, neuroscientist Matthew Stanford presents a model that helps make sense of these types of discoveries. Stanford points out that Scripture teaches that human beings are created as both material and immaterial beings, possessing a physical body and nonphysical mind and spirit. Instead of being a “ghost in the machine,” our material and immaterial natures are intertwined, interacting with each other. It is through our bodies (including our brain), that we interact with the physical world around us. The activities of our brain influence the activities of our mind (where our thoughts, feelings, and emotions are housed), and vice versa. It is through our spirit that we have union with God. Spiritual transformation can influence our brain’s activities and how we think; also, how and what we think can influence our spirit.

So, in light of Stanford’s model, we can make sense of how love can be both a physical and spiritual experience while preserving the biblical view of human nature.

Smells Like Intelligent Design

Clearly, the attraction between two people extends beyond body odor and other physical processes and features. Still, the connection between body odor and the composition of the MHC genes presents itself as an ingenious, elegant way to ensure that animal populations (and human beings) are best positioned to withstand the assaults of pathogens. As an old-earth creationist, this insight is exactly what I would expect, attracting me to the view that life on Earth, including human life, is the product of Divine handiwork.

Now, I am off to the chocolatier to get my wife a box of her favorite chocolates for Valentine’s Day. I don’t want her to decide that I stink as a husband.

Resources

Reprinted with permission by the author
Original article at:
https://www.reasons.org/explore/blogs/the-cells-design/read/the-cells-design/2018/02/14/love-is-in-the-air-and-it-smells-like-intelligent-design