B cells, often described as the body’s antibody factories, produce the antibodies that help protect us from infections. As part of our adaptive immune system, B cells can also form our immune memory, allowing the body to respond faster and more effectively when it encounters the same threat again. Until now, it was not recognized that so much of the immune memory we carry as adults may already be shaped in the first days of life.
“After birth, the immune system is shaped by microbes and environmental exposures,” says Joan Yuan, associate professor at Lund University and head of the Developmental Immunology research group at the Lund Stem Cell Center. “What we show is that some of this early immune experience is stored in a long-lived population of B-1 cells, which were not previously considered a major memory compartment.”
The researchers show that B-1 cells formed shortly after birth carry memory like features and persist into adulthood, arising at a stage of life not previously considered to contribute significantly to adult immune memory.
Using lineage-tracing, a technique that allows researchers to track the developmental history and fate of individual cells over time, together with immunization experiments, the team showed that the memory of early-life microbial encounters can be stored within the B‑1 cell compartment which persists into adulthood.
“Across multiple tissues and B-cell subsets, early-life-derived B cells consistently showed molecular and functional features associated with antigen experience, or in other words, immune memory, rather than a naïve state,” continues Joan Yuan.
Linking early life immune memory to leukemia risk
Because memory B cells are designed to be long lived, the researchers next asked whether this early layer of memory could also influence disease later in life. They focused on chronic lymphocytic leukemia (CLL), a slow developing blood cancer that primarily affects older adults and is known to arise from B cells with characteristics strikingly similar to B-1 cells.
“CLL is an age associated disease, and its origin has been debated for many years,” explains Niklas Segrén, doctoral student at Lund University and first author of the study. “There has been evidence pointing to immune memory-like cells, and also to early developmental origins, but it has been difficult to connect these ideas directly.”
To follow early‑life B cells over time, the researchers used a genetic “time‑stamping” approach that marks B cells based on when they are generated during development. By combining this system with a mouse model of CLL, the team was able to track immune cells in their natural developmental context and distinguish early‑life B cells from those generated later, even in adult animals.
“This allowed us to link early B cell waves to a disease that emerges much later in life,” explains Niklas Segrén. “We found that the leukemia was driven specifically by B-1 cells that developed before postnatal day 10. These early life memory B cells expanded slowly over time and eventually gave rise to a CLL-like disease in aging mice.”
What this could mean for human disease
The researchers also compared their findings with published human datasets. They found similarities between the early‑life B‑1 cells identified in mice and gene expression patterns observed in human CLL, supporting the idea that comparable mechanisms may exist in people.
At the same time, the authors emphasize the limitations. “We cannot prove this conclusively in humans,” says Niklas Segrén. “But the molecular similarities suggest that early immune programming could be relevant for understanding at least some forms of human CLL.”
The researchers also note that early life B-1 cells are likely beneficial for most of life, contributing to immune regulation and suppression of inflammation. “The increased cancer risk may be a trade off that only becomes apparent at very old age,” says Joan Yuan.
A new way to think about immune development
The study builds on a series of earlier discoveries from Joan Yuan and her team, which has previously shown how early immune programming affects long term immune health.
“The findings highlight developmental timing as an important dimension by which to understand the complexity of the immune system,” says Joan Yuan. “Instead of seeing the immune system as a snapshot in adulthood, we argue for understanding the design logic of its layered formation. The developmental history of the immune system gives us an evolutionarily relevant lens to dissect both normal immune function and disease.”
