While working on mapping every cell in the human body, scientists discovered an elusive type of immune cell emerging for the first time 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 arise early in mouse development, in the womb, and they produce different antibodies when activated. Some of these antibodies attach to the mouse’s own cells and help remove 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 bacteria†
After the discovery of B-1 cells in mice, a research group reported in 2011 that they had found similar cells in humans, but these results were not accepted as conclusive evidence. “At that time there was back and forth… Not everyone agreed with our profile of human B-1 cells,” says Dr. Thomas Rothstein, a professor and founder of the Division of Investigative Medicine and director of the Center for Immunobiology at Western Michigan University Homer Stryker MD School of Medicine, who was senior author of that earlier work.
Now, a new study, published Thursday (May 12) in the journal Scienceprovides solid evidence that B-1 cells arise in early human development, in the first and second trimester† “It confirms and expands on the work we’ve published before,” Rothstein, who was not involved in the new research, told Live Science.
“I think this is the most compelling data yet” supporting the idea that humans carry B-1 cells, said Dr. Nicole Baumgarth, a professor at the UC Davis Center for Immunology and Infectious Diseases, who was not involved 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 developing immune system
The new research is published alongside three other studies recently conducted by the Human Cell Atlas (HCA) consortium, an international research group investigating the position, function and characteristics of each cell type in the human body. Together, the four studies — all published May 12 in Science — include analyzes of more than 1 million human cells, representing more than 500 different cell types sampled from more than 30 different tissues.
“You can think of it as a ‘Google Maps’ of the human body, and it’s really that ‘street map view’ of the individual cells and where they are in tissues that we’re aiming for,” said study senior author Sarah Teichmann, lead of Cellular Genetics at the Wellcome Sanger Institute in England and co-chair of the Human Cell Atlas Organizing Committee.
In helping build this atlas of the human body, Teichmann and her colleagues recently focused their efforts on: immune cells, and in particular the immune cells that arise during early human development. Through this work, they discovered evidence of human B-1 cells. “What we’re showing is that they do indeed exist in humans,” Teichmann said at a press conference on May 10.
The analyzes included 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 keeps the embryo inside. early pregnancy† All tissue samples analyzed by the team were from the Human Developmental Biology Resource, a tissue bank in the UK that stores human embryonic and fetal tissues, with written consent from donors. They also used publicly available data from previous HCA studies.
In total, the data covered an early developmental period ranging from four to 17 weeks after conception, i.e. within the first and second trimesters.
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The researchers took high-resolution snapshots of these tissues, at a 0.001 inch (50 microns) scale, which is thinner than a human hair, Teichmann said at the news conference. And on a single-cell level, the team analyzed all “RNA transcripts” in each tissue, which reflect the different proteins each cell makes. Using these transcripts, the researchers were able to draw conclusions about the identity and function of each cell.
Through this detailed analysis, the team discovered cells that matched the description of B-1 cells found in mice, both in their characteristics and the timing of their emergence.
“In the mouse system, the B-1 cells arise early — they occur first,” Rothstein said. Another type of immune cell, aptly called B-2, then appears after the first B-1 cells and eventually becomes the most abundant form of B cell in the mouse. The new study suggests something similar is happening in humans, where B-1 cells arise and are most common in early development, Rothstein told Live Science.
What purpose can these special cells serve in a developing human? They can help form new tissues as they form, Teichmann said.
“If you think about fetal development, in general there’s a massive remodeling of tissues that happens all the time,” Baumgarth said. For example, people initially develop a tissue between their fingers, but this tissue is cut back before birth. It may be that B-1 cells help cut tissue during development, but “that’s speculation on my part,” she said.
In addition to sculpting tissues, the B-1 cells can provide some degree 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 develop initially and could lay the groundwork for future studies of how the cells function later in life, Rothstein said.
Originally published on Live Science.