Highly Effective Memory B Cells Localized in the Lungs

Researchers showed that memory B cells can be localized in the lungs. © Adobe Stock

How can we increase the efficacy of vaccines used to protect against viral respiratory diseases such as influenza and COVID-19?  Scientists from Inserm, CNRS and Aix-Marseille Université at the Center of Immunology Marseille-Luminy are opening up new prospects in the field, with the triggering of memory B cells directly in the lungs looking to be a promising avenue. At present, the vaccines are administered intramuscularly and do not trigger the appearance of these cell populations. This research, which enhances fundamental knowledge in the field of immunology, has been published in the journal Immunity.

Memory B cells are immune cells produced primarily in the lymph nodes and spleen following infection. They persist for a long time in these regions and retain the memory of the infectious agent. If the body is confronted with the same agent in the future, these cells are immediately mobilized and rapidly reactivate the immune system for effective protection of the individual.

Following extensive research into these memory B cells, researchers discovered three years ago that they could also be localized in the lungs. The team led by Inserm researcher Mauro Gaya and his colleagues from the Center of Immunology Marseille-Luminy (AMU/CNRS/Inserm) and the Center for Immunophenomics (AMU/CNRS/Inserm) went further in order to describe the nature and functioning of this specific immune cell population.

The aim was to better understand these cells and their involvement in the long-term immune response against respiratory infections. For this, the scientists worked with two mouse models of infection: the influenza and Sars-CoV-2 viruses.


“Bona fide” and “bystanders”

They used fluorescent markers to track the appearance of memory B cells after infection, following which they performed a single-cell transcriptome analysis[1]. “These techniques enabled us to precisely localize these cells in the lungs of our animal models and describe their gene expression profile cell by cell to study their function,” explains Gaya.

Approximately ten weeks after inoculation of the virus and after its elimination from the body, the team observed the formation of groups of memory B cells in the bronchial respiratory mucosa, in a strategic position allowing them to be directly in contact with any new virus entering the lungs.

Furthermore, this research suggests that there are two subpopulations of memory B cells expressing different genes, known as “bona fide” and “bystanders”, with the “bona fide” cells having a particular affinity for the virus that triggered their appearance. In the event of new encounters with this pathogen, they immediately differentiate into plasma cells[2] and secrete highly specific antibodies against the virus.

Conversely, the “bystanders” do not directly recognize the virus but bind thanks to a specific receptor to the immune complexes formed by the antibodies that are produced by the “bona fides”.

The “bystanders” can therefore enable cross-reactions by increasing the response of different “bona fide” populations against several types of viruses. “What we have is a two-tier system that enables a synergistic effect and increases the efficacy of the anti-viral memory response in the lungs,” explains Gaya.

In addition to advancing fundamental knowledge in immunology, the research team sees in these findings a longer-term way of improving the efficacy of influenza or COVID-19 vaccines.

These findings could in fact form the basis for new research into the way vaccines are administered. “The hypothesis is that by intranasal vaccination, we could mimic the natural entry pathway of the virus, mobilize these lung memory B cells to block the virus as soon as it reaches the respiratory tract in the event of an infection. In this way, we could combat severe forms and also better protect against infection,” concludes Gaya.


[1] Single-cell transcriptome analysis: a technique used to study the genes expressed in each cell of a sample

 [2] Plasma cells:B cells that have reached a stage of terminal differentiation during which they produce antibodies

Lancement de la campagne de recherche participative Science à la Pelle : trouver des médicaments sous nos pieds

Even at Low Doses, Exposure to the Endocrine Disruptor DEHP Impairs Tooth Development

Sagittal section of the incisor of a mouse exposed to DEHP

Sagittal section of the incisor of a mouse exposed to DEHP showing delayed mineralization of the developing enamel, the brown layer between the protein matrix (pink) and the dentin (green). © Sylvie Babajko/Inserm

Some endocrine disruptors have already been associated with an impaired quality of tooth enamel. After demonstrating the harmful effects of bisphenol A on tooth development, a team of researchers from Inserm, Université Paris Cité and Sorbonne Université, at the Cordeliers Research Center in Paris, in collaboration with CNRS[1] went on to look at the effects of DEHP, an endocrine disruptor in the phthalate family, on dental development. While the use of DEHP is highly regulated, it still continues to be found in food containers and certain medical devices such as neonatal intensive care equipment. The scientists have shown that the teeth of mice exposed daily to low doses of this substance present defects whose intensity and prevalence depend on the exposure dose and sex of the animal, with males being more likely than females to develop dental impairments. This discovery confirms the relevance of considering dental enamel defects as an early marker of exposure to environmental toxins. This study has been published in Environmental Health Perspectives.

The significant environmental changes of recent decades have impacted the health and well-being of human populations and all living organisms. Finding markers of exposure to the toxic substances present in the environment therefore represents a major challenge for research.

The scientific literature suggests that dental enamel could be one such marker.

Its analysis enables, for example, retrospective evaluation of the environmental conditions, either by identifying the presence of pollutants trapped in the mineral or by distinguishing enamel defects linked to alterations in cell activity occurring during its formation.

Exposure to endocrine disruptors such as bisphenol A has already been associated with one type of enamel defect, molar incisor hypomineralization (MIH), which is found in around 15% of children between 6 and 8 years of age. Other substances are being monitored, such as the endocrine disruptor DEHP which, despite regulations and bans, can still be present in many medical devices, including neonatal intensive care unit equipment[2].

DEHP belongs to the family of phthalates, chemical compounds commonly used to make plastics flexible. Phthalates can be found in food containers, consumer goods, toys, cosmetics and medical devices. 

On November 23, 2021[3], the European Commission published Regulation no. 2021/2045 amending Annex XIV by adding endocrine disrupting properties to DEHP, BBP, DBP and DIBP. As a result of these changes, certain previously exempt uses are now subject to authorization, including “medical devices and food contact materials that contain DEHP“.

Given the widespread presence of DEHP, its potential contamination of children (whose teeth are still forming), and previous data on the effects of certain endocrine disruptors on enamel, researchers from Inserm, Université Paris Cité and Sorbonne Université, at the Cordeliers Research Center, in collaboration with CNRS, wished to explore the potential effects of DEHP.

In this mouse study, the scientists observed the effects of daily exposure to DEHP, at both low and higher doses. These doses were equivalent to those that can be found in the context of environmental exposure:

  • 5 micrograms/kilo/day: estimated daily exposure of a child to DEHP;
  • 50 micrograms/kilo/day: level of exposure in hospitalized patients on infusion or dialysis, for example.

After 12 weeks of exposure, defects were noted on the rodents’ incisors – teeth that have the particularity of continuous growth[4] and represent the ideal experimental model for studying developing dentition. Less mineralized and softer, the teeth of the exposed mice reflected impaired enamel quality, which worsened as the level of exposure to DEHP increased.

To supplement these data, the researchers then observed the effects of this exposure to DEHP at the cellular and molecular levels. They identified delayed enamel mineralization associated with altered expression of the key genes in enamel formation. Another particularity of the study was that the scientists compared the impact of exposure according to sex and observed greater susceptibility in males.

DEHP therefore disrupted the development of enamel in mice by acting directly on the dental cells, and with increased prevalence and severity in males.

Finally, the scientists point out that the effects observed on the growing teeth of rodents exposed to DEHP or bisphenol A are similar in terms of impaired enamel quality and greater susceptibility of males, and differ in terms of the cells targeted and the molecular mechanisms involved.

While these experimental data need to be consolidated, they do suggest that DEHP, like bisphenol A, could also contribute to enamel hypomineralization defects such as MIH.

“We know that the perinatal period and the first years of life are crucial to child development and health in adulthood. Dental enamel could be a very early reflection of the environmental conditions at this point in life,” explains Sylvie Babajko, Inserm Research Director and last author of the study.

For the research team, the next step is now to understand the effects of combinations of different classes of molecules – or “cocktail effects” – on dental health.


1 Contributors to these findings: Laboratory of Molecular Oral Pathophysiology (Cordeliers Research Center/INSERM/Université Paris Cité/Sorbonne Université), Laboratory for Biomedical Research in Odontology (BRIO, UPR2496/Université Paris Cité), Institute of Physical Chemistry (ICP, CNRS/Université Paris-Saclay), Paris-Saclay Laboratory of Mechanics (LMPS, CNRS/CentraleSupélec/ENS Paris-Saclay), and Paris Seine Neuroscience Laboratory at the Paris Seine Institute of Biology (IBPS, CNRS/Inserm/Sorbonne Université).

2 Malarvannan G, Onghena M, Verstraete S, et al. Phthalate and alternative plasticizers in indwelling medical devices in pediatric intensive care units. J Hazard Mater. 2019; doi:10.1016/j.jhazmat.2018.09.087


4 The teeth of these animals continue to grow throughout their lives, unlike human teeth.

One in Four French Adults Thought to Have Some Form of Hearing Loss

This hearing loss study is based on data from thousands of participants from the Constances cohort. © Adobe Stock

Hearing loss is a public health problem that affects billions of people worldwide. However, data on its prevalence – generally speaking, its frequency in the population – and on the use of hearing aids, remain imprecise. A new study by a research team from Inserm and Université Paris Cité at the Paris Cardiovascular Research Center (PARCC, Inserm unit 970)[1], in collaboration with the Paris Hospitals Group AP-HP and Foch Hospital in Suresnes, shows for the first time that 25% of adults in France are affected by some form of hearing loss. Disabling hearing loss, which is more severe, is thought to affect 4% of adults. This prevalence varies with age and other factors (standard of living, noise exposure at work, cardiovascular diseases, etc.), which are described in the study. In addition, the scientists have found that hearing aids remain largely underused, especially among seniors. These findings, based on data from thousands of participants from the Constances cohort, have been published in JAMA Open Network.

Hearing loss affects around 1.5 billion people worldwide, with World Health Organization (WHO) projections suggesting an increase to 2.5 billion by the year 2050. This is a major public health problem, especially since hearing loss is associated with decreased quality of life, social isolation, and other health problems such as depression, cognitive decline, and dementia.

However, it is still difficult to fully understand the extent of the problem and to improve prevention and screening measures, because the data available on the exact prevalence of hearing loss, the characteristics of those affected, and the use of hearing aids are still scarce.

They are most often derived from studies with small and nonrepresentative samples of participants from which it is complicated to draw generalizations, and from self-reported, unmeasured hearing loss data.

In order to have more robust data which can be used to inform public policy, a research team from Inserm, Paris Public Hospitals Group AP-HP, Université Paris Cité and Foch Hospital assessed the prevalence of hearing loss in France. For this they used data from 186,460 volunteers from the Constances cohort, who are representative of the general adult population and in whom hearing loss was measured using hearing tests.

The Constances cohort

Constances is a large-scale French epidemiological cohort, composed of a representative sample of 220,000 adults aged 18 to 75 years at the time of their inclusion. The participants are asked to have a health check every four years and to complete an annual questionnaire. Each year, their data are matched with the French national health insurance databases. This large-scale cohort is supported by the National health insurance fund and financed by the Investments for the future program.

The data collected, which concern health, socio-professional characteristics, use of health care services, and biological, physiological, physical, and cognitive parameters, enable us to learn more about the determinants of many diseases.

For more information:

The volunteers, aged 18 to 75 years, completed questionnaires on their demographic and socioeconomic characteristics, their medical history and that of their relatives, as well as their lifestyles. They also underwent a health examination, between 2012 and 2019, which included a hearing test.

The study authors analyzed the entirety of this data and found that 25% of the individuals in the study sample had hearing loss, with 4% of the sample affected by disabling hearing loss (see box below). In addition, this research found that little use is made of hearing aids. For example, only 37% of patients with disabling hearing loss were wearing one.

Hearing loss

  • The term “hearing loss” is used to refer to a person who is unable to hear as well as someone with normal hearing, the threshold being 20 decibels (dB) of loss in the better ear.
  • “Disabling hearing loss” means a hearing loss greater than 35 decibels (dB) in the better ear.

Taking their interpretation further, the researchers then attempted to identify the factors associated with hearing loss. Their analyses suggest that older people, men, people with a high body mass index (BMI), people with diabetes, with cardiovascular risk factors, a history of depression, or exposed to noise at work had the highest likelihood of suffering from hearing loss.

Conversely, having a higher income or education level, living alone, or living in an urban area were associated with a lower likelihood of hearing loss.

Hearing aid use was particularly low among elderly people (who are proportionately more affected by disabling hearing loss), men, smokers, and those with a high BMI.

Improving our understanding of the prevalence of hearing loss and the profile of those it affects is very important if we are to better target patients who are at risk, in order to screen them, improve their care, and refine prevention measures.

“This is the first time in France that a study on the prevalence of hearing loss and the use of hearing aids has been conducted on such a large and representative sample of the country’s adult population. This allows us to establish a reliable picture and to provide keys to public decision-makers, even though effective solutions (such as hearing aids and cochlear implants) are available to manage this major health problem,” stress Quentin Lisan and Jean-Philippe Empana, who coordinated the study.

While France has recently passed a measure allowing the reimbursement of hearing aids by Social Security (which was not yet the case at the time the study was conducted), it would be interesting for future research to evaluate the efficacy of such an initiative in encouraging the use of hearing aids.


[1] Team 4: Integrative Epidemiology of Cardiovascular Disease

Researchers described how the cerebellum modulates our ability to socialize

This image of the cerebellum of a mouse expressing a fluorescent protein in Purkinje cells expressing dopamine D2 receptors © Emmanuel Valjent, Institut de Génomique Fonctionnelle (Montpellier)

The cerebellum is essential for sensorimotor control but also contributes to higher cognitive functions including social behaviors. In a recent study, an international research consortium including scientists from Inserm – University of Montpellier (France), the Institut de Neurociències Universitat Autònoma de Barcelona (INc-UAB) (Spain), and the University of Lausanne (Switzerland) uncovered how dopamine in the cerebellum modulates social behaviors via its action on D2 receptors (D2R). By using different mouse models and genetic tools, the researchers’ work shows that changes in D2R levels in a specific cerebellar cell type, the Purkinje cells, alter sociability and preference for social novelty without affecting motor functions. These new findings pave the way to determine whether socially related psychiatric disorders, such as autism spectrum disorders (ASD), bipolar mood disorder, or schizophrenia, are also associated with altered dopamine receptors expression in specific cerebellar cell types.

Dopamine (DA) neurons are a major component of the brain reward system. By encoding motivational value and salience, they tighly regulate motivation, emotional states and social interactions. Although the regulation of these processes has been largely ascribed to neural circuits embedded in limbic regions, recent evidence indicate that the cerebellum, a region primarily involved in motor control, may also contribute to higher cognitive functions including social behaviors. However, whether cerebellar dopamine signaling could participate to the modulation of these functions remained unexplored. Researchers from Inserm – Montpellier University (France), the Institut de Neurociències UAB (Spain), and the University of Lausanne (Switzerland) uncovered a new role for dopamine as modulator of social behaviors in the mouse cerebellum.

By combining cell type-specific transcriptomics, immunofluorescence analyses and 3D imaging, researchers first demonstrated the presence of dopamine D2 receptors (D2R) in Purkinje cells (PCs), the output neurons of the cerebellar cortex. Using patch-clamp recordings, they were able show D2R modulated synaptic excitation onto PCs. “This first set of results was already determinant for us, as they unveiled that D2R were present in the cerebellum and that, despite their low expression level, they were functional”, highlights Dr Emmanuel Valjent, research director at Inserm (France), and coordinator of the study.

The researchers then went on to study their functions. By using genetic approaches to invalidate or overexpress D2R selectively in PCs, they analyzed the impact of these alterations on motor and non-motor cerebellar functions. “We have uncovered an unexpected causal link between PCs D2R expression levels right in the center of the cerebellum, the Crus I/II lobules, and the modulation of social behaviors. Reducing the expression of this specific dopamine receptor impaired the sociability of mice as well as their preference for social novelty, while  their coordination and motor functions remained unaffected” explains Dr. Laura Cutando, Marie-Curie researcher at the Mitochondrial Neuropathology research group at INc-UAB, and first author of the article.

This study constitutes a first step towards a better understanding of the role of dopamine in the cerebellum and the mechanisms underlying psychiatric disorders such as schizophrenia, ADHD and anxiety disorders, which have all in common aberrant DA signaing and altered social behaviors.