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Mutations and Environment Shape Immunity in Infancy

B cell
The new study analyzes how B cells change in early childhood, affecting immunity, infection and allergies. | NIAID

New research has revealed that certain environmental conditions and mutations in antibodies are associated with an increased risk of allergic diseases such as eczema in newborns.

In the new study, published in the February 27 issue of Science Translational Medicine, scientists followed the children from infancy through the first three years of life and analyzed how environmental variables such as the presence of pets as well as changes in their immune system correlated with allergic diseases and infections. The results offer a detailed look at how these factors shape the development of immunity in children, helping to address a longstanding question in the field of allergy research.

Allergic diseases such as food allergy and eczema have become increasingly common in children over the past several decades. A 2013 survey from the CDC found that the prevalence of food allergies in children increased from 3.4% to 5.1% between 1997 and 2011, and the prevalence of skin allergies jumped from 7.4% to 12.5% in the same time period.

Although the causes of this increase remain unclear, some scientists suspect that a lack of exposure to bacteria early on life due to increased hygienic standards could promote the excessive immune reactions seen in allergies, a theory referred to as the "hygiene hypothesis."

To resolve this mystery, researchers have begun to investigate how environmental and hygienic conditions can affect immunity in children. Much of their efforts have focused on B cells, which are the main producers of the body's protective antibodies and contain a diverse population of B cell receptors, molecules that are present on the cell's surface.

B cell receptors undergo a process known as somatic hypermutation when they are exposed to antigens, or molecules that activate the immune system. This process in turn influences how B cells produce and release antibodies, allowing the immune system to adapt to new threats.

Scientists believe that somatic hypermutation triggered by exposure to viruses, bacteria and environmental factors shapes how B cell receptors and antibody variants mature in infants and young children, in turn affecting the risk of developing allergic conditions that feature abnormal immune responses.

"It is now clear that environmental exposures in the first years of life, such as the kinds of foods eaten or viruses encountered, can shape lifelong immune responses and affect one's risk of developing immunological diseases like peanut allergy," said Scott Boyd, associate professor in the department of pathology at Stanford University and senior author of the new study.

To get a better idea of how the B cells that produce antibodies change in early life, the research team examined several types of antibodies and the composition of B cell receptors in a group of young children raised in different household environments.

They studied 51 children from birth to three years of age and collected blood samples from the subjects either once or at two or three yearly time points. The scientists then performed genetic sequencing on the blood samples to measure how antibody genes and B cells changed in response to antigen exposure.

The sequencing revealed that children with certain health conditions had higher mutation rates in several common antibody types. For example, children with more frequent somatic hypermutation in two antibodies named IgD and IgM demonstrated higher rates of upper respiratory infections, indicating these antibody types play a key role in responding to infectious diseases, according to Boyd.

Furthermore, children with disrupted skin structure due to eczema or allergies also had elevated somatic hypermutation frequencies in a third antibody named IgE, which is central to allergic reactions.

These findings, "fit with some prior thinking about the relationship between eczema and the development of other allergies such as food allergies," according to Boyd, and reveal a new mechanism by which the IgE antibody could become better at binding to foreign molecules and potentially triggering allergies.

Boyd also cautions that further research will be needed to explore the relationship between IgE-expressing B cell development and disrupted skin barriers in infancy.

During the study, the researchers also recorded how the household environment varied among the study subjects. They tracked variables such as whether the household contained any pets, how clean the household was, and whether the households used antimicrobial cleaning products.

Children growing up in households with cleaning products containing the antimicrobial chemicals triclosan and triclocarban had higher mutation frequencies in IgE, IgD and IgG antibodies. However, usage of these products was not associated with a different rate of infections or allergies, and the authors found no link between pet ownership and differences in antibody mutations.

Ultimately, the scientists believe their results will serve as an important reference for future studies of immune responses throughout human life. Boyd believes their observations could assist researchers who study the effects of other variables on immune cells, such as how childhood exposure to a specific strain of the flu shapes responses to other flu strains later in life.

Author

Joseph Cariz

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