Nav: Home

On the origin of B1 cells

February 14, 2019

A new MDC study may resolve a decades-old debate in immunology: A team led by Prof. Klaus Rajewsky reports in Science that distinct progenitor cells are not required for the development of B1 cells. Instead, the team's experiments show that B1-typical B-cell receptor can reprogram B2 cells into B1 cells, suggesting that B1 cells emerge as a consequence of their special B-cell receptors.

In the fight against diseases, one thing is absolutely vital: B-cells. These particular cells, which belong to a class of white blood cells called lymphocytes, are the only cells in the immune system capable of making antibodies. The Y-shaped proteins latch onto foreign structures such as bacteria or viruses, thus marking them as intruders for elimination by phagocytes and other immune cells.

B1 cells are already present in newborns and play an important role in natural immunity

There are two types of B cells. B2 cells, which make up the largest portion of the white blood cells in the body, mainly circulate in the blood and in the lymphoid organs such as the thymus, spleen, lymph nodes, and bone marrow. B1 cells, on the other hand, are mainly present in the peritoneal and pleural cavities, and hence in the areas around the intestinal tract and the lungs. They respond to a wide range of foreign proteins, called antigens, but also to some of the body's own antigens - and in a different manner than the highly specialized B2 cells.

B1 cells constitute the majority of all B lymphocytes in newborns, but in adults the proportion of B1 cells drops to only a few percent. This is one of the reasons why B1 cells are considered carriers of natural immunity - i.e. the innate immune system - while B2 cells are mainly responsible for adaptive immunity, which emerges, for example, after an infection or a vaccination.

For decades, immunologists have debated the origin of B cells

Until now, it was unclear how the different types of B cells developed. "Some immunologists think B1 and B2 cells emerge from different progenitor cells," says Dr. Robin Graf, one of the lead authors of the Science article and a member of the Immune Regulation and Cancer research group at the Max Delbrück Center for Molecular Medicine (MDC) in Berlin, which is headed by Prof. Klaus Rajewsky. "Other immunologists believe special autoreactive B-cell receptors trigger the formation of B1 cells."

The new study, in which also other scientists from Rajewsky's group who were at the time in Cologne and Boston played a major role, now provides clear evidence for the validity of the second hypothesis. "We replaced the B-cell receptor in mature B2 cells with a B1-typical B-cell receptor, which is found in nature only on B1 cells," explains Graf.

The manipulated B2 cells assumed the properties of B1 cells

This procedure transformed the B2 cells into B1 cells. "We were able to show that the cells acquired the B1-typical surface markers," reports Graf. The manipulated B2 lymphocytes also took on the functional properties of B1 lymphocytes. "When we transplanted them into mice, they were homing to those parts of the body where B1 cells are naturally found," says the MDC researcher.

In addition, the cells began to spontaneously produce antibodies. "That's also a typical feature of B1 cells," explains Graf. What's more, once the B1-typical receptor was expressed on the B2 lymphocytes, the cells started to multiply in great numbers over a period of one to two weeks. This strikingly resembles the natural development of B1 cells at early stages - a process that has barely been studied.

The end to a longstanding debate is in sight

Later in the study, Graf measured the activity of thousands of genes in the manipulated B2 cells. "Here we found that the same genes were active in these cells as in normal B1 cells," reports the scientist.

Graf expects that the new study will convince immunologists that B1 cells emerge as a consequence of the specificity of their B-cell receptors.

R. Graf et al. (2019): "BCR-dependent lineage plasticity in mature B cells." Science. DOI: 10.1126/science.aau8475

The Max Delbrück Center for Molecular Medicine (MDC)

The Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC) was founded in Berlin in 1992. It is named for the German-American physicist Max Delbrück, who was awarded the 1969 Nobel Prize in Physiology and Medicine. The MDC's mission is to study molecular mechanisms in order to understand the origins of disease and thus be able to diagnose, prevent, and fight it better and more effectively. In these efforts the MDC cooperates with the Charité - Universitätsmedizin Berlin and the Berlin Institute of Health (BIH) as well as with national partners such as the German Center for Cardiovascular Research and numerous international research institutions. More than 1,600 staff and guests from nearly 60 countries work at the MDC, just under 1,300 of them in scientific research. The MDC is funded by the German Federal Ministry of Education and Research (90 percent) and the State of Berlin (10 percent), and is a member of the Helmholtz Association of German Research Centers.

Max Delbrück Center for Molecular Medicine in the Helmholtz Association

Related Progenitor Cells Articles:

Nutrient deficiency in tumor cells attracts cells that suppress the immune system
A study led by IDIBELL researchers and published this week in the American journal PNAS shows that, by depriving tumor cells of glucose, they release a large number of signaling molecules.
Scientists modify CAR-T cells to target multiple sites on leukemia cells
In a preclinical study, scientists engineer new CAR-T cells to attack three sites on leukemia cells, instead of one.
UCLA study links progenitor cells to age-related prostate growth
The prostates of older mice contain more luminal progenitor cells -- cells capable of generating new prostate tissue -- than the prostates of younger mice, UCLA researchers have discovered.
Dead cells disrupt how immune cells respond to wounds and patrol for infection
Immune cells prioritise the clearance of dead cells overriding their normal migration to sites of injury.
Transplanted bone marrow endothelial progenitor cells delay ALS disease progression
Transplanting human bone marrow-derived endothelial progenitor cells into mice mimicking symptoms of amyotrophic lateral sclerosis (ALS) helped more motor neurons survive and slowed disease progression by repairing damage to the blood-spinal cord barrier, University of South Florida researchers report.
Revealed: How the 'Iron Man' of immune cells helps T cells fight infection
The immune system's killer T cells are crucial in fighting viral infections.
White blood cells related to allergies may also be harnessed to destroy cancer cells
A new Tel Aviv University study finds that white blood cells which are responsible for chronic asthma and modern allergies may be used to eliminate malignant colon cancer cells.
Conversion of breast cancer cells into fat cells impedes the formation of metastases
An innovative combination therapy can force malignant breast cancer cells to turn into fat cells.
Researchers develop a new method for turning skin cells into pluripotent stem cells
Researchers at the University of Helsinki, Finland, and Karolinska Institutet, Sweden, have for the first time succeeded in converting human skin cells into pluripotent stem cells by activating the cell's own genes.
Interrupted reprogramming converts adult cells into high yields of progenitor-like cells
A modified version of iPS methodology, called interrupted reprogramming, allows for a highly controlled, safer, and more cost-effective strategy for generating progenitor-like cells from adult cells.
More Progenitor Cells News and Progenitor Cells Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Listen Again: Reinvention
Change is hard, but it's also an opportunity to discover and reimagine what you thought you knew. From our economy, to music, to even ourselves–this hour TED speakers explore the power of reinvention. Guests include OK Go lead singer Damian Kulash Jr., former college gymnastics coach Valorie Kondos Field, Stockton Mayor Michael Tubbs, and entrepreneur Nick Hanauer.
Now Playing: Science for the People

#562 Superbug to Bedside
By now we're all good and scared about antibiotic resistance, one of the many things coming to get us all. But there's good news, sort of. News antibiotics are coming out! How do they get tested? What does that kind of a trial look like and how does it happen? Host Bethany Brookeshire talks with Matt McCarthy, author of "Superbugs: The Race to Stop an Epidemic", about the ins and outs of testing a new antibiotic in the hospital.
Now Playing: Radiolab

Dispatch 6: Strange Times
Covid has disrupted the most basic routines of our days and nights. But in the middle of a conversation about how to fight the virus, we find a place impervious to the stalled plans and frenetic demands of the outside world. It's a very different kind of front line, where urgent work means moving slow, and time is marked out in tiny pre-planned steps. Then, on a walk through the woods, we consider how the tempo of our lives affects our minds and discover how the beats of biology shape our bodies. This episode was produced with help from Molly Webster and Tracie Hunte. Support Radiolab today at