Publisher Health

The health benefits of dietary fiber vary across individuals and may depend on the specific type of fiber and the dose consumed, researchers report April 28th in the journal Cell Host & Microbe.
“Our results demonstrate that the physiological, microbial, and molecular effects of individual fibers differ substantially,” says senior study author Michael Snyder, a geneticist at Stanford School of Medicine. “Further, our results demonstrate the tantalizing prospect of using targeted fibers, mediated by the microbiome, to drive health and systems biology in a predictable, personalized direction.”
High-fiber diets reduce the risk of heart attack, stroke, and cardiovascular disease. They act by lowering cholesterol and promoting a healthier lipid profile for people eating a Westernized diet. Dietary fibers are carbohydrates that are selectively metabolized by gut microbes but are otherwise indigestible by humans. Understanding how they affect the microbiome and in turn human biochemistry and physiology is critical for effectively using dietary fiber supplementation to improve human health.
Chemically, fibers are diverse in length, branching, solubility, charge, and other properties. “They are usually studied as complex mixtures from their plant source,” Snyder says. “There is a need for determining the unadulterated effects of individual fibers on the microbiome and for establishing associated health biomarkers, ideally by testing different fibers on the same individuals.”
To address this need, Snyder and his colleagues set out to understand how purified individual fiber components affect the same group of participants. Specifically, they investigated the physiological effects of dietary supplementation with two common and structurally distinct soluble fibers: arabinoxylan (AX), which is common in whole grains, and long-chain inulin (LCI), which is found in onions, chicory root, and Jerusalem artichokes.
The researchers used stool metagenomics, plasma proteomics, metabolomics, lipidomics, and analyzed serum cytokines and clinical values in 18 participants. “Fiber is associated with improved metabolic and cardiovascular health, but understanding the effects of individual fibers on microbial and metabolomic response has not been studied using a multiomics dataset,” Snyder says.
The participants consumed 10 grams of fiber per day during the first week, 20 grams per day during the second week, and 30 grams per day during the third week. The results revealed fiber- and often dose-dependent microbial and systemic responses. On average, AX consumption was associated with a significant reduction in low-density lipoprotein (LDL), known as the bad cholesterol, and an increase in bile acids, which may be contributing to the cholesterol reduction. Yet individual responses varied, and some participants saw little to no change in cholesterol levels.
“Several high-fiber foods have cholesterol-reducing effects, and our study suggests that these reductions may be driven by individual constituents of the mix of fibers in unrefined plant foods,” Snyder says.
Meanwhile, LCI was associated with a modest decrease in inflammation markers and an increase in the abundance of Bifidobacterium — a generally beneficial type of gut microbe known to produce healthy short-chain fatty acids. But at the highest dose, there was an increase in inflammation and levels of a liver enzyme called alanine aminotransferase, suggesting that too much of this fiber may be harmful. Again, these potentially negative responses were variable across the participants.
Two limitations of the study were its short duration and the small number of participants. But according to the authors, the study provides insights into mechanisms behind fiber-induced cholesterol reduction, reveals the deleterious effects of high inulin consumption, and highlights the association of individual, purified fibers with the microbiome.
“Overall, our findings show that the benefits of fiber are dependent on fiber type, dose, and participant — a landscape of factors resulting from interactions between fiber, the gut microbiome, and host,” Snyder says. “These results have important implications in personalized response and interventions.”
Funding was provided by the National Institutes of Health and the National Center for Complementary and Integrative Health. The authors declare no competing interests.
Story Source:
Materials provided by Cell Press. Note: Content may be edited for style and length.

As race season approaches, many runners have the same goal: go faster. But in a study publishing April 28 in the journal Current Biology, researchersshow that speeding up might require defying our natural biology. By combining data from runners monitored in a lab along with 37,000 runs recorded on wearable fitness trackers, scientists have found that humans’ natural tendency is to run at a speed that conserves caloric loss — something that racers seeking to shave time off their miles will have to overcome.
The research group, composed of scientists from Queens University in Ontario and Stanford University in California, have been studying the mechanics of running in labs for 15 years but hadn’t gotten a chance to study running in the wild before now. “We were able to fuse the two datasets to gain new insights and combine the more messy wearable data with the gold standard lab experiments to learn about how people run out in the world,” says co-author Jennifer Hicks, deputy director of Stanford’s Wu Tsai Human Performance Alliance.
What surprised the team most was the consistency that they found across the combined datasets. “We intuitively assume that people run faster for shorter distances and then would slow their pace for longer distances,” says first author Jessica Selinger, a neuromechanics researcher at Queens University. But this wasn’t the case. Most of the runners analyzed stuck with the same speed, whether they were going for a short run or a long haul over ten kilometers.
From an evolutionary perspective, it makes sense that people would run at the speed that uses the least amount of energy. This caloric conservation is something that has been observed across the animal kingdom. But in the modern world, humans’ reasons for running have changed, and if the goal is speed, there are some tricks runners can use.
“Listening to music with a faster pace has been shown to help speed up stride frequency, which can then increase running speed,” said Selinger. In addition, picking faster running buddies can give you a boost.
Selinger and Hicks hope that having large pools of fitness data from wearables will help researchers to gain insights about populations. “You can look at connections with the built environment and access to recreation resources and start to layer all of that data to really understand how to improve physical activity and health more broadly,” says Hicks.
This work was supported by funding from the Natural Sciences and Engineering Research Council of Canada, the National Institutes of Health, the Wu Tsai Human Performance Alliance, and the Joe and Clara Tsai Foundation.
Story Source:
Materials provided by Cell Press. Note: Content may be edited for style and length.

A team led by scientists at the University of Illinois Urbana-Champaign tracked the rise and fall of SARS-CoV-2 in the saliva and nasal cavities of people newly infected with the virus. The study was the first to follow acute COVID-19 infections over time through repeated sampling and to compare results from different testing methodologies.
The findings are reported in the journal Nature Microbiology.
“We capture the most complete, high-resolution, quantitative picture of how SARS-CoV-2 replicates and sheds in people during natural infection. There are no other data like this,” said U. of I. microbiology professor Christopher B. Brooke, who led the research with microbiology and statistics professor Pamela P. Martinez and pathobiology professor Rebecca L. Smith. “The study sheds light on several aspects of infection that were poorly understood, that are important for both public health purposes as well as just fundamental biology.”
The study grew out of the SHIELD: Target, Test, Tell initiative, the U. of I.’s COVID-19 response program, which began testing staff, students and faculty members twice per week in fall 2020. Illinois researchers realized that the testing data could be a treasure trove of information about the course of infection: for example, how fast different SARS-CoV-2 variants replicated, and how individuals differed in their ability to clear the infection. The team received Institutional Review Board approval to pursue such a study.
The National Institutes of Health stepped in to fund the effort to compare PCR tests, which amplify and detect viral RNA, with rapid antigen tests, which look for proteins associated with the virus. This funding made other aspects of the study possible.
Starting within 24 hours of an initial positive test, the team took daily nasal and saliva samples from adults who tested positive for COVID-19 infection. The 60 participants in the study ranged from 19 to 73 years old. The study followed each person up to 14 days.

Examining a range of research from studies in laboratory animals to epidemiological research in human populations gives scientists a clearer picture of what kind of nutrition can offer the best chance for a longer, healthier life, said USC Leonard Davis School of Gerontology Professor Valter Longo.
In an article that includes a literature review published April 28 in Cell, Longo and coauthor Rozalyn Anderson of the University of Wisconsin describe the “longevity diet,” a multi-pillar approach based on studies of various aspects of diet, from food composition and calorie intake to the length and frequency of fasting periods.
“We explored the link between nutrients, fasting, genes, and longevity in short-lived species, and connected these links to clinical and epidemiological studies in primates and humans, including centenarians,” Longo said. “By adopting a multi-system and multi-pillar approach based on over a century of research, we can begin to define a longevity diet that represents a solid foundation for nutritional recommendation and for future research.”
What — and when — to eat for longevity
Longo and Anderson reviewed hundreds of studies on nutrition, diseases and longevity in laboratory animals and humans and combined them with their own studies on nutrients and aging. The analysis included popular diets such as the restriction of total calories, the high-fat and low-carbohydrate ketogenic diet, vegetarian and vegan diets, and the Mediterranean diet.
The article also included a review of different forms of fasting, including a short-term diet that mimics the body’s fasting response, intermittent fasting (frequent and short-term) and periodic fasting (two or more days of fasting or fasting-mimicking diets more than twice a month). In addition to examining lifespan data from epidemiological studies, the team linked these studies to specific dietary factors affecting several longevity-regulating genetic pathways shared by animals and humans that also affect markers for disease risk, including levels of insulin, C-reactive protein, insulin-like growth factor 1, and cholesterol.

Seven hours is the ideal amount of sleep for people in their middle age and upwards, with too little or too much little sleep associated with poorer cognitive performance and mental health, say researchers from the University of Cambridge and Fudan University.
Sleep plays an important role in enabling cognitive function and maintaining good psychological health. It also helps keep the brain healthy by removing waste products. As we get older, we often see alterations in our sleep patterns, including difficulty falling asleep and staying asleep, and decreased quantity and quality of sleep. It is thought that these sleep disturbances may contribute to cognitive decline and psychiatric disorders in the aging population.
In research published today in Nature Aging, scientists from the UK and China examined data from nearly 500,000 adults aged 38-73 years from the UK Biobank. Participants were asked about their sleeping patterns, mental health and wellbeing, and took part in a series of cognitive tests. Brain imaging and genetic data were available for almost 40,000 of the study participants.
By analysing these data, the team found that both insufficient and excessive sleep duration were associated with impaired cognitive performance, such as processing speed, visual attention, memory and problem-solving skills. Seven hours of sleep per night was the optimal amount of sleep for cognitive performance, but also for good mental health, with people experiencing more symptoms of anxiety and depression and worse overall wellbeing if they reported sleeping for longer or shorter durations.
The researchers say one possible reason for the association between insufficient sleep and cognitive decline may be due to the disruption of slow-wave — ‘deep’ — sleep. Disruption to this type of sleep has been shown to have a close link with memory consolidation as well as the build-up of amyloid — a key protein which, when it misfolds, can cause ‘tangles’ in the brain characteristic of some forms of dementia. Additionally, lack of sleep may hamper the brain’s ability to rid itself of toxins.
The team also found a link between the amount of sleep and differences in the structure of brain regions involved in cognitive processing and memory, again with greater changes associated with greater than or less than seven hours of sleep.
Having a consistent seven hours’ sleep each night, without too much fluctuation in duration, was also important to cognitive performance and good mental health and wellbeing. Previous studies have also shown that interrupted sleep patterns are associated with increased inflammation, indicating a susceptibility to age-related diseases in older people.
Professor Jianfeng Feng from Fudan University in China said: “While we can’t say conclusively that too little or too much sleep causes cognitive problems, our analysis looking at individuals over a longer period of time appears to support this idea. But the reasons why older people have poorer sleep appear to be complex, influenced by a combination of our genetic makeup and the structure of our brains.”
The researchers say the findings suggest that insufficient or excessive sleep duration may be a risk factor for cognitive decline in ageing. This is supported by previous studies that have reported a link between sleep duration and the risk of developing Alzheimer’s disease and dementia, in which cognitive decline is a hallmark symptom.
Professor Barbara Sahakian from the Department of Psychiatry at the University of Cambridge, one of the study’s authors, said: “Getting a good night’s sleep is important at all stages of life, but particularly as we age. Finding ways to improve sleep for older people could be crucial to helping them maintain good mental health and wellbeing and avoiding cognitive decline, particularly for patients with psychiatric disorders and dementias.”
The research was supported by the National Key R&D Program of China, the Shanghai Municipal Science and Technology Major Project, the Shanghai Center for Brain Science and Brain-Inspired Technology, the 111 Project, the National Natural Sciences Foundation of China and the Shanghai Rising Star Program.
Story Source:
Materials provided by University of Cambridge. The original text of this story is licensed under a Creative Commons License. Note: Content may be edited for style and length.

Since ancient times, our gut microbiome, home to a vast number of bacteria, viruses, fungi, and other microorganisms, has been thought to influence many aspects of human health. Most recently, sequencing technology has shown that it may also play a role in the treatment of cancer. A review paper published in JAMA Oncology by investigators from Brigham and Women’s Hospital captures the current understanding of the connection between the gut microbiome and therapeutic response to immunotherapy, chemotherapy, cancer surgery and more, pointing to ways that the microbiome could be targeted to improve treatment.
“We know that a healthy gut is key to our overall health,” said lead author Khalid Shah, MS, PhD, of the Center for Stem Cell and Translational Immunotherapy in the Department of Neurosurgery at the Brigham. “Our gut is so important that we often refer to it as our ‘second’ brain. In recent years, we’ve begun to appreciate the many roles of the gut, including the gut-brain connection and the connection between the gut and our immune system. Conversely, gut dysfunction or dysbiosis can have a negative effect on our health.”
Shah and colleagues report on an emerging role for gut microbiota in immunotherapy. Immune checkpoint inhibitors and immune checkpoint blockade therapy are novel strategies for treating cancer, but response to these forms of treatment varies considerably between individuals and across cancer types. Several studies have found differences in the species of bacteria found in fecal samples from responders and non-responders, suggesting that different microbiome compositions may influence clinical responses. Other studies suggest that diet and probiotics — live bacterial species that can be ingested — as well as antibiotic medications and bacteriophages can influence the composition of the gut microbiome and, in turn, a response to immunotherapy. In particular, the authors highlight recent studies on the effects of ketogenic diets for patients with cancer.
“Today, developing treatments that sync immunotherapies and gut microbiota provides medicine a unique opportunity to truly effect change in patient care,” said Shah.
The authors also provide an overview of how microbiota have been implicated in influencing response to chemotherapy and other conventional cancer treatments as well as how cancer therapies may reciprocally affect the microbiome and cause side effects.
“Overall, these findings support the potential of influencing the gut microbiota to diminish the side effects of conventional cancer treatment,” said Shah.
The authors note that there is little understanding of what the “ideal” bacteria consortia in the gut looks like and how findings from preclinical models may or may not translate into applications in humans. They note that caution must be exercised before using probiotics or making dietary changes. Many cancer clinical trials are currently exploring the influence of the microbiome to help address some of the limitations and gaps in understanding. These include trials of fecal microbial transplantation, dietary supplements and novel drugs that may influence microbiota composition.
“There is strong evidence that the gut microbiome can have a positive influence on cancer therapies,” said Shah. “There remain exciting possibilities to explore, including the influence of healthy diet, probiotics, novel therapies, and more.”
Disclosures: Shah owns equity in and is a member of the Board of Directors of AMASA Therapeutics, a company developing stem cell-based therapies for cancer; Shah’s interests were reviewed and are managed by Brigham and Women’s Hospital and Partners HealthCare in accordance with conflict-of-interest policies. No other disclosures were reported.
Story Source:
Materials provided by Brigham and Women’s Hospital. Note: Content may be edited for style and length.

There are cells in the body known as pluripotent stem cells that are yet to specialize in a particular biological function. These cells maintain the potential to become any of the possible cell types in an organism. Pluripotent stem cells have shown great promise in fields such as regenerative and transplant medicine for their properties, including unlimited self-renewal. The protein NANOG is the telltale marker of pluripotent stem cells and a necessary ingredient to reset specialized cells back into naïve, untrained stem cells. How human NANOG accomplishes this feat remains largely a mystery.
Researchers at Baylor College of Medicine and collaborating institutions report in the journal Nature Cell Biology insights into the mechanism of how human NANOG facilitates the activation of cell pluripotency. The team discovered that NANOG’s ‘super stickiness’ enables it to form large aggregates at very low concentrations. These aggregates interact with chromatin — strings of DNA and proteins that coil to form chromosomes carrying the cells’ genetic information — to reshape the genomic landscape in a way that activates a pluripotent state.
“Resetting specialized cells to a pluripotent state requires massive reorganization of the chromatin and changes in gene expression — turning on genes involved in pluripotency and turning off genes that specify specialized cells,” said corresponding author Dr. Josephine Ferreon, assistant professor of pharmacology and chemical biology and member of the Dan L Duncan Comprehensive Cancer Center at Baylor. “Furthermore, coordinated gene activation often requires bringing DNA elements that are far apart closer to enable gene expression. We found that NANOG’s properties — its naturally floppy, flexible 3D shape and a C-terminal tail that is structurally akin to prion-like proteins — enable it to achieve this.”
Studying NANOG poses significant challenges
NANOG’s high tendency to self-adhere and aggregate poses a problem for traditional ensemble techniques that require high protein concentrations. To study this very challenging protein, the team resorted to highly sensitive fluorescence approaches.
“In this study, we applied single molecule and fluorescence fluctuation microscopy techniques with which we can visualize whether two molecules interact with each other. The experiments were performed at very small concentrations, picomolar to nanomolar, where we can usually avoid aggregation and investigate highly aggregation-prone proteins,” said co-corresponding author Dr. Allan Chris Ferreon, assistant professor of pharmacology and chemical biology at Baylor. “However, with NANOG, even at extremely low concentrations, we still detected aggregation. Nonetheless, we were able to show that NANOG aggregation is actually essential to its function as a master transcription factor and a mediator of the bridging of DNAs. This phenomenon may be unique to NANOG.”
“We think that this phenomenon is the reason why NANOG expression is key to the establishment of pluripotency. When NANOG’s level is low, cells are prone to differentiate, and when its level is high, the ground pluripotent state or ‘full reset’ is achieved and maintained,” Dr. Josephine Ferreon said.
NANOG aggregates are similar to those of amyloids, which are culpable for Alzheimer’s disease and other neurodegenerative disorders. However, in NANOG’s case, the aggregates are not associated with a harmful condition, but with an essential cellular process, the activation of cell pluripotency. A growing body of scientific evidence suggests that not all amyloids are harmful, some can be rather functional. More and more of these amyloid-forming prion-like proteins are found to be molecular players of cellular functions such as gene expression, chromatin condensation and cell signaling.
The researchers think that NANOG acts like a molecular glue that can initiate and stabilize key chromatin interactions important for the pluripotent state. NANOG’s aggregation behavior also explains its role as a molecular ‘hub’ protein and its interactions with many important chromatin regulators that are involved in opening chromatin and recognizing and modifying specific chromatin regions.
“In the future, we hope to understand more about the role of NANOG and its prion-like region in recruiting or cooperating with important transcription factors, coactivators and epigenetic modulators to reshape the genomic landscape,” Dr. Josephine Ferreon said.
Other contributors to this work include Kyoung-Jae Choi, My Diem Quan, Chuangye Qi, Joo-Hyung Lee, Phoebe S. Tsoi, Mahla Zahabiyon, Aleksandar Bajic, Liya Hu, B. V. Venkataram Prasad, Shih-Chu Jeff Liao and Wenbo Li.
This work was supported by an NIGMS, NIH grant (R01 GM122763), NINDS, NIH grant (R01 NS105874, R21 NS107792 and R21 NS109678) and a Cancer Prevention and Research Institute of Texas (CPRIT) Scholarship. Part of this work is supported by the NIH ”4D Nucleome” program (U01HL156059), NIGMS (R21GM132778, R01GM136922), CPRIT (RR160083, CPRIT RP180734), the Welch foundation (AU-2000-20190330) and UTHealth Innovation for Cancer Prevention Research Training Program Postdoctoral Fellowship (CPRIT RP210042). Further support was provided by the Eunice Kennedy Shriver National Institute of Child Health & Human Development of the National Institutes of Health under award number P50HD103555.
Story Source:
Materials provided by Baylor College of Medicine. Original written by Molly Chiu. Note: Content may be edited for style and length.

Certain childhood tumors have an extreme need for amino acids. Scientists at the Hopp Children’s Cancer Center Heidelberg (KiTZ), the German Cancer Research Center (DKFZ), the University of Heidelberg, and HI-STEM* gGmbH have now discovered the molecular mechanisms underlying this and how the cancer cells could be turned off.
The Hopp Children’s Cancer Center Heidelberg (KiTZ) is a joint institution of the German Cancer Research Center (DKFZ), Heidelberg University Hospital (UKHD) and the University of Heidelberg (Uni HD).
Every year, approximately one in 100,000 children develops a new neuroblastoma, often in the first year of life. This makes neuroblastomas a relatively common group of tumors in children. They form in immature nerve tissue during embryonic development and occur mainly in the adrenal gland, spine, neck, chest, abdomen, and pelvis. Neuroblastomas are difficult to treat and often resistant to therapy. Infants and young children are particularly affected. In some cases, the tumor regresses completely without any therapy. In about half of the patients, however, it progresses inexorably despite highly intensive therapy.
An important regulator that determines the direction in which the disease develops is the cancer gene MYCN. Only recently it became known that this cancer gene sets the course for whether precursor cells develop into mature nerve cells or become malignant neuroblastoma cells. Neuroblastomas with unfavorable progression also carry hundreds of active copies of the MYCN gene in their genome. The high MYCN activity leads to profound changes in the metabolism of the cancer cells, because MYCN in turn switches on and off a large number of other genes. But what advantage does this give the cancer cell, and can this highly specialized network be specifically disrupted to actively fight the cancer cells?
These were the questions asked by the team of scientists led by Frank Westermann of the Hopp Children’s Cancer Center Heidelberg (KiTZ) and the German Cancer Research Center (DKFZ), Andreas Trumpp, DKFZ and HI-STEM* gGmbH, and Thomas Höfer of DKFZ. In the present study, first authors Hamed Alborzinia and Andres Florez discovered that neuroblastoma cells with high MYCN activity need one thing in particular: the amino acid cysteine. Cysteine is an important building block for most cellular proteins and lipids. The fast-growing cancer cells need large amounts of these building blocks to produce new cells.
At the same time, cancer cells need cysteine to protect themselves from naturally occurring toxic peroxides that are produced conditionally by their highly active metabolism. “The cysteine hunger of neuroblastoma cells is so great that they use two pathways to obtain cysteine,” says Sina Kreth, another first author of the study. “They use the import of the amino acid and additionally crank up an alternative synthetic pathway to obtain cysteine from the amino acid methionine,” first author Lena Brückner adds.
However, it is precisely these adaptation processes that make the neuroblastoma cells sensitive. If the scientists deprived them of cysteine, the MYCN-driven tumor cells could no longer inactivate the toxic peroxides produced and died by ferroptosis, a special form of cell death. The research team then tested whether this process could be a potential Achilles heel for a therapy against malignant neuroblastoma in mice.
The scientists deliberately turned off the tap to the tumors: They blocked cysteine uptake, cysteine synthesis, and also switched off a key enzyme that normally prevents cancer cells from poisoning themselves with peroxides. The cancer cells then initiated their own self-destruction through ferroptosis, and the tumors shrank.
“Ferroptosis cell death was discovered only a few years ago, and the results now show for the first time not only in cell cultures but also in cancer-bearing mice how this process can be manipulated to kill highly aggressive human neuroblastoma cells by inducing ferroptosis,” Hamed Alborzinia emphasizes.
The findings also provide a possible explanation for why some neuroblastomas with moderate MYCN activity in infants and young children simply disappear in some cases: “Cells basically take up less cysteine in the first years of life. Therefore, when they start to divide uncontrollably, they soon run out of cysteine reserves and ferroptotic cell death is initiated,” Andres Florez explains. Some neuroblastomas without MYCN activity cannot escape this self-destruction and then simply die after a certain time when cysteine becomes scarce.
For high-risk patients with high MYCN activity, the study provides the first insights into how the balance between cysteine uptake, production, and consumption could possibly be disturbed in such a way that these cells also initiate their self-destruction. Whether the newly discovered principle will also prove effective in the therapy of neuroblastoma patients must now be tested in clinical trials.
* The Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM) gGmbH was founded in 2008 as a public-private partnership by the DKFZ and the Dietmar Hopp Foundation.

Massachusetts General Hospital (MGH) researchers have developed a novel treatment strategy that has the potential to bring the life-saving benefits of chimeric antigen receptor T-cell therapy (CAR T) to patients with acute myeloid leukemia (AML) the most common form of leukemia in adults.
The method involves a combination of drug therapy to expand the number of targets on tumor cells, and an engineering approach to help the therapy adhere more tightly and durably to those targets.
They describe their work in a study published online in the journal Cancer Cell.
CAR T therapy has revolutionized the care of patients with advanced cancers of the blood system. It involves harvesting a patient’s T cells, which are key components of the immune system, and genetically engineering them to recognize a specific target (antigen) on the surface of cancer cells. The cells are then expanded in the laboratory and returned to the patient’s bloodstream, where they mount an enhanced tumor-killing immune response.
CAR T therapy relies on the ability of T cells to identify antigens that are either unique to cancer cells or are present in much greater numbers on normal cells than on malignant cells.
For lymphoid malignancies such as acute lymphoblastic leukemia and B-cell lymphomas, which arise from white blood cells, targeting tumors can also deplete the population of normal antibody-producing B cells, but clinicians can compensate for the loss of normal cells by replacing immunoglobulins that B cells normally make.