Memory B cells (MemB) are a major component of humoral immune memory, apart from long-lived plasma cells. They are the cellular basis for long-term immune protection after infection or vaccination. Immune memory is a key feature of the adaptive immune system, where antigen receptors undergo somatic V(D)J gene rearrangement for specific antigen recognition. Therefore, cells carrying specific BCR or TCR genes are the carriers of adaptive immune memory. Additionally, it has been found that innate immune cells can also exhibit a form of memory, showing a significantly enhanced effect upon re-infection. This type of innate immune memory is sometimes called "trained immunity."

Recent studies on the role of epigenetics in cell fate determination and transgenerational stable inheritance have led to the exploration of the contribution of epigenetics to the formation of innate immune memory, and how epigenetic memory is realized is becoming an important research direction.

On March 29, 2024, the research teams led by Prof. HOU Baidong and Prof. ZHU Bing from the Institute of Biophysics at the Chinese Academy of Sciences published a research paper in Science Advances. The paper, which studied the epigenetic information in anti-viral MemB, found that anti-viral MemB exhibits characteristics of both adaptive immune memory and innate immune memory.

To study the formation mechanism of anti-viral Mem B, the researchers used a virus-like particle (Qβ-VLP) derived from bacteriophage Qβ as a model antigen in mice, which induces a long-lasting germinal center (GC) response. The Qβ-VLP induced MemB was stable in mice for over a year. It also bound to antigens with high affinity, much similar to MemB identified in humans.

To investigate the epigenetic changes during the formation of these cells and their contribution to MemB cell function, the researchers used methods such as RNA-seq and ATAC-seq to analyze antigen-specific B cells isolated at different stages of activation after immunization, as well as memB cells after re-immunization. The study found that in the secondary response, MemB exhibited enhanced transcription of a group of genes, which was related to gain of chromatin accessibility in resting MemB. This indicates that epigenetic memory may contribute to the enhanced expression of these genes. Moreover, Qβ-VLP induced secondary response MemB was enriched with more virus response related genes compared to regular protein antigens. This enhanced innate immune response may protect virus-specific memory B cells from destruction.

Since innate immunity is an ancient form of immunity in evolution, this study demonstrated that B cells still retains the immune memory strategy of innate immune cells after acquiring the ability of V(D)J gene rearrangement. This reflects the biological evolution and adaptation to the environment. This study provides an initial insight into the process of epigenetic memory formation in anti-viral MemB, offering clues for exploring the mechanism of long-lasting immune memory formation.

This work was supported by the National Key Research and Development Program of China, and the National Natural Science Foundation of China.

Figure. Epigenetic alterations predispose Q + MemB to enhanced transcription of anti-viral genes upon antigen re-challenge.

(Image by HOU Baidong's group)

Article link: https://www.science.org/doi/10.1126/sciadv.adk0858

Contact: HOU Baidong

Institute of Biophysics, Chinese Academy of Sciences

Beijing 100101, China

E-mail: baidong_hou@ibp.ac.cn

(Reported by Prof. HOU Baidong's group)