Memory B cells (MemB) are a primary component of humoral immune memory besides long-lived plasma cells, serving as the cellular basis for long-term immune protection following infection or vaccination. Immune memory is a crucial feature of the adaptive immune system, where antigen receptors undergo somatic V(D)J recombination for specific antigen recognition, making cells carrying specific BCR or TCR genes the carriers of adaptive immune memory. Additionally, it has been observed that innate immune cells can exhibit a form of memory, manifesting as significantly enhanced effector responses upon reinfection, sometimes referred to as "trained immunity." With recent studies focusing on the role of epigenetics in cellular fate determination and intergenerational stable inheritance, exploration into the contribution of epigenetic inheritance to the formation of innate immune memory is becoming an important research direction.
On March 29, 2024, in a collaborative effort published in Science Advances by the research groups of Hou Baidong and Zhu Bing from the Institute of Biophysics, Chinese Academy of Sciences, titled "Anti-viral memory B cells exhibit enhanced innate immune response facilitated by epigenetic memory," it was discovered that antiviral MemB cells possess characteristics of both adaptive and innate immune memory.
To investigate the formation mechanism of antiviral MemB cells, the research group led by Hou Baidong previously utilized virus-like particles derived from the bacteriophage Qβ (Qβ-VLP) as a model antigen in mice. These particles could induce long-lived germinal center (GC) reactions, and the MemB cells induced by Qβ-VLP remained stable in mice for over a year, exhibiting high affinity binding to antigens, similar to those identified in humans.
In order to study the changes in epigenetic information during the formation of these cells and their contribution to MemB cell function, the research groups of Hou Baidong and Zhu Bing collaborated to analyze the functionality of memory B cells through RNA-seq, ATAC-seq, and other methods following antigen re-immunization in vivo. The study found that during secondary responses, there was an increase in the proportion of genes undergoing transcriptional enhancement in MemB cells, which was associated with increased chromatin accessibility in resting MemB cells, indicating that epigenetic changes may initiate the expression of these genes. Furthermore, MemB cells from secondary responses induced by Qβ-VLP enriched more virus response-related genes compared to those induced by conventional protein antigens, with most of these genes being associated with innate immune signal transduction. This enhanced innate immune response may protect virus-specific memory B cells from destruction.
As innate immunity represents a more ancient form of immunity in evolution, the adaptive immune system, even after acquiring the ability of V(D)J recombination, still partially retains the immune memory mechanism of innate immune cells, reflecting the adaptation of organisms to their environment during evolution. This study provides initial insights into the formation of epigenetic memory in antiviral MemB cells, offering clues for exploring the mechanism of long-lasting immune memory formation.
The changes observed in the graph suggest an enhancement in the transcription of antiviral genes when Qβ+ MemB encounters the antigen again.
Dr. Zhu Xiping, Associate Researcher Hong Sheng, and Assistant Researcher Bu Jiachen from the Institute of Biophysics, Chinese Academy of Sciences, are the co-first authors of the paper. Researcher Hou Baidong, Researcher Zhu Bing, and Associate Researcher Hua Zhaolin are the corresponding authors. This research received funding from the National Key R&D Program and the National Natural Science Foundation of China.
Article link: https://www.science.org/doi/10.1126/sciadv.adk0858
