Behe’s B Cell Bravado, Part 1

| By Kathryn Applegate on Endless Forms Most Beautiful

Behe’s B Cell Bravado, Part 1


In my last couple of posts, we examined a classic example of evolution in action—the production and selection of antibodies. Evolution in the body is a documented reality, but how did the process for generating antibodies come about in the first place?

Intelligent Design proponent Michael Behe says scientists don’t have the faintest idea. In his 1996 book Darwin’s Black Box, he laments, “Although great strides have been made in understanding how the immune system works, we remain ignorant of how it came to be” (136). As evidence, he cites two brief articles (in his view, the field’s “best efforts”) before dismissing their conclusions out of hand. He continues, “We can look high or we can look low, in books or in journals, but the result is the same. The scientific literature has no answers to the question of the origin of the immune system” (138).

But is science really silent on this topic? So much blood, sweat, tears, and NIH money have been spent on the study of the immune system that a complete lack of answers about its beginnings would, as Behe suggests, mean doom for evolutionary theory. The truth is, according to Web of Science, even by 1996 hundreds of peer-reviewed papers had been published on the subject, each contributing a tiny piece to the overall puzzle.

Quick review: components of the antibody diversity system

Behe argues that three aspects of the immune system—clonal selection, antibody diversity, and the complement system—are irreducibly complex and pose “massive challenges to a putative step-by-step evolution” (138).

Because we have already examined how antibody diversity is generated, we will limit our discussion to the evidence for how this ingenious system might have arisen. Much more could be said about other aspects of the innate and adaptive immune responses.

Recall that the genome contains several clusters of gene segments (red and green in the figure below), each of which has tens to hundreds of members. In B cells, proteins encoded by two Recombination ActivatingGenes (RAGs; blue) join together one member from each of the clusters by excising the DNA between them. The genome of each B cell is thus irreversibly altered in a unique way, depending on which segments are joined, such that the recombined gene segments code for the antigen-binding site of that B cell’s antibody.

RAG1 and RAG2 can’t bind just anywhere on the DNA; they recognize special sequences called Recombination Signal Sequences (RSSs; orange and yellow). RSSs are found flanking each gene segment, similar to special cues we use in grammar like capitalized words at the start of sentences and punctuation marks at the end. The RAG proteins home in on two randomly-chosen RSSs, bring them physically close to one another, and cleave the double-stranded DNA at both gene-RSS junctions. DNA repair machinery then repairs the break, joining the two gene segments together and the two RSSs together. The closed loop of DNA containing the RSSs gets removed, while the recombined gene is now ready to code for an antibody..

Behe’s mistaken assumptions

Behe argues that a minimally functional antibody diversity system needs three components: the antibody genes themselves, start and stop signals (like RSSs), and machinery to cleave and rejoin the DNA at the signals (like RAG and the DNA repair proteins). He can’t imagine how a multi-component system could have arisen by a gradual process, because each component is dependent on the other two for the whole shebang to work.

From the start, Behe makes the faulty assumption that antibody receptors incapable of recombination would be useless. He writes:

A primitive system with only one or a few antibody molecules would be like the propeller turning at one revolution per day: not sufficient to make a difference... Because the likelihood is so small for the shape of one antibody being complementary to the shape of a threatening bacterium—perhaps one in a hundred thousand or so—an animal that spent energy making five or ten antibody genes would be wasting resources..." (130-1).

What Behe fails to recognize is that many, many receptors in the immune system do their jobs without gene arrangements. These receptors bind to molecules commonly found on the surface of harmful microbes. In fact, some 90% of animal species on the planet don’t even have adaptive immunity, so antibody production by a gene rearrangement mechanism cannot be imperative for life (though humans and other vertebrates are quite dependent on it now). Contrary to Behe’s assumption, the first antibody genes could easily have had useful functions without RSSs and RAGs.

A family of molecules called the Toll-like receptors (TLRs) demonstrates the utility of having an all-purpose microbe detector that does not require millions of randomly-generated variants. TLRs, located on the surface of special immune cells in the blood, recognize bacterial cell walls and virus-specific DNA sequences, causing an all-out attack by the body on the foreign invader. In the process, some of the host tissue gets destroyed, but this collateral damage is a necessary cost to slow down the infection.

This so-called innate immune response—the first line of defense—occurs immediately upon infection, while antibodies take several days to produce. Without innate immunity, the animal might die before antibodies even have a chance to work. The fact that virtually all multi-cellular organisms have TLRs indicates how critical they are to survival.

If innate immunity is so effective that 90% of animals live just fine without adaptive immunity, it’s natural to wonder why some animals do have it. A major advantage it provides is an immunological “memory” of past infections, making it easier to fight off similar pathogens in the future. (Vaccines work on this principle—by exposing the body to inactivated or dead viruses, we give B cells a “heads up” so they can make and store antibodies before the real thing hits.) Antibodies also enable targeted killing of the pathogen, preventing further damage to the host by the non-specific innate immune response.

There’s another way to ask why some animals have an adaptive immune response: rather than seek to explain what added function or advantage it serves, we can ask about the mechanism by which it came to be in the first place. That will be our topic in my next post


Bottaro, Andrea, Inlay, Matt A., and Matzke, Nicholas J. “Immunology in the spotlight at the Dover 'Intelligent Design' trial.” Nature Immunology. 7(5), 433-435. May 2005.

Inlay, Matt. "Evolving Immunity: A Response to Chapter 6 of <em.darwin's black="" em="">".

Travis, John. “On the Origin of the Immune System.” Science. 324(5927), 580-582. May 2009.


About the Author

Kathryn Applegate

Kathryn Applegate is Program Director at BioLogos. She received her PhD in computational cell biology at The Scripps Research Institute in La Jolla, Calif. At Scripps, she developed computer vision software tools for analyzing the cell's infrastructure, the cytoskeleton.