While working to map each cell of the human body, scientists have discovered an elusive type of immune cell that first emerges in the womb. The existence of such cells in humans has been hotly debated – until now.
These mysterious cells, known as B-1 cells, were first discovered in mice in the 1980s, according to a 2018 review in The Journal of Immunology. These cells appear early in mouse development, in the uterus, and they produce various antibody when activated. Some of these antibodies attach to the mouse’s own cells and help clear dying and dead cells from the body. Activated B-1 cells also make antibodies that act as a first line of defense against pathogens, such as viruses and bacteria.
After the discovery of B-1 cells in mice, a research group reported in 2011 that they had found equivalent cells in humans, but these results have not been accepted as conclusive evidence. “At that time there was back and forth… Not everyone agreed with our profile of human B-1 cells,” said Dr. Thomas Rothstein, founding professor and director of the Department of Medicine at research and director of the Center for Immunobiology at Western Michigan University Homer Stryker MD School of Medicine, who was the senior author of this previous work.
However, a new study, published Thursday, May 12 in the journal Scienceprovides strong evidence that B-1 cells emerge early in human development, in the first and second trimester. “This confirms and extends the work that we have published previously,” Rothstein, who was not involved in the new research, told Live Science.
“I think this is the most conclusive data to date” supporting the idea that humans carry B-1 cells, said Dr. Nicole Baumgarth, a professor at the Center for Immunology and Infectious Diseases at the Institute. UC Davis, which did not participate in the new study. In theory, these cells may play a critical role in early development, and by studying them further, scientists can better understand what healthy immune system development looks like in humans, Baumgarth told Live Science.
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A rare look at the development of the immune system
The new research was published alongside three other studies recently conducted by the Human Cell Atlas (HCA) consortium, an international research group working to determine the position, function and characteristics of each type of cell in the human body. Together, the four studies — all published May 12 in Science — include analyzes of more than one million human cells, representing more than 500 distinct cell types taken from more than 30 different tissues.
“You can think of it as a ‘Google Maps’ of the human body, and it’s really this ‘road map view’ of individual cells and where they are in the tissues that we’re aiming for,” said L. study lead author Sarah Teichmann, director of cell genetics at the Wellcome Sanger Institute in England and co-chair of the Human Cell Atlas Organizing Committee.
By participating in the construction of this atlas of the human body, Teichmann and his colleagues have recently focused their efforts on immune cells, and in particular the immune cells that emerge early in human development. It was through this work that they discovered evidence of human B-1 cells. “What we’re showing is that they do exist in humans,” Teichmann said during a May 10 press briefing.
The analyzes looked at cells from nine developing tissues, such as the thymus, a gland that makes immune cells and hormones, and the embryonic yolk sac, a small structure that nourishes the embryo in early pregnancy. All tissue samples analyzed by the team came from the Human Developmental Biology Resource, a tissue bank in the UK that stores human embryonic and fetal tissue, with written permission from the donors. They also incorporated publicly available data from previous HCA studies.
In total, the data covered an early period of development ranging from four to 17 weeks after fertilization, i.e. during the first and second trimesters.
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The researchers took high-resolution snapshots of these tissues, at the scale of 0.001 inches (50 microns), which is thinner than a human hair, Teichmann said at the press conference. And at a single cell level, the team analyzed all of the “RNA transcripts” in each tissue, which reflect the different proteins each cell makes. Using these transcripts, researchers were able to make inferences about each cell’s identity and function.
Through this detailed analysis, the team spotted cells that matched the description of B-1 cells found in mice, both in terms of their attributes and when they emerged.
“In the mouse system, B-1 cells appear early — they appear first,” Rothstein said. A different type of immune cell, appropriately called B-2, then emerges after the first B-1 cells and eventually becomes the most abundant form of B cell in mice. The new study suggests something similar is happening in humans, where B-1 cells appear and are most abundant early in development, Rothstein told Live Science.
What might these special cells be used for in a developing human being? They can help sculpt new tissue as it forms, Teichmann said.
“When you think about fetal development, in general, there’s massive tissue remodeling happening all the time,” Baumgarth said. For example, humans initially develop webbing between their fingers, but this webbing is severed before birth. It may be that B-1 cells help direct such tissue cutting during development, but “that’s speculation, on my part,” she said.
In addition to tissue sculpting, B-1 cells may provide some level of immune protection against pathogens small enough to cross the placental barrier, Baumgarth said. Again, this is speculation, she said.
The new study expands our understanding of how B-1 cells initially develop and could lay the groundwork for future studies of how the cells function later in life, Rothstein said.
Originally posted on Live Science.