Nature Immunology: Identification of long-lived plasma cell taxa

On October 31, 2022, the Qi Hai Research Group of the Institute of Immunology, School of Medicine, Tsinghua University, and Wang Jianbin's Research Group, School of Life Sciences, Tsinghua University, published an online publication entitled "Heterogeneous plasma cells and long-lived subsets in response to immunization, autoantigen" in the journal Nature Immunology and microbiota", which systematically describes the heterogeneity of mouse plasma cells and long-lived plasma cell groups
of different sources and subtypes.

Longevity plasma cells are highly specialized antibody-secreting cells living in the bone marrow, which, once induced, can provide the human body with antibody protection for decades to life, and is an important part of
humoral immune memory.
However, due to their scarcity and lack of known surface molecular markers, long-lived plasma cells are poorly
understood.
By sequencing the spleen and bone marrow plasma cells of mice at the transcriptome and antibody molecular levels, the researchers classified these cells in detail for the first time and identified the long-lived plasma cell taxa
.

The researchers found that different long-lived plasma cells have different molecular markers, suggesting that these cells have diversified differentiation pathways
.
Among them, long-lived plasma cells secreting IgG and IgM had the phenotype of EpCAMhiCXCR3- compared with short-acting plasma cells secreting these two antibodies.
Long-lived IgA-secreting plasma cells can be distinguished
from other IgA plasma cells by the phenotype of Ly6AhiTigit-.
In addition, the researchers found that the antibody molecules of different plasma cell groups have different characteristics: IgG long-lived plasma cells and some IgA long-lived plasma cells can be induced by exogenous antigen immunity or viral infection, and the antibody molecules secreted by them contain high-frequency somatic hypermutations, suggesting that they have undergone affinity maturation in germinal centers; In contrast, IgM long-lived plasma cells lack somatic hypermutations and can be produced normally in mice without T cells, indicating that their production does not depend on germinal center responses
.
Interestingly, these cells contain antibody molecules that recognize antigens from their own and gut flora and can be shared by different mice, suggesting that they have the characteristics
of innate immune cells.

The above work reveals the molecular characteristics of long-lived plasma cells, indicating that they can differentiate from both germinal centers and innate immune B cells, thereby deepening our understanding of the conditions for the production of long-lived plasma cells and laying a foundation
for further study of their differentiation and maintenance mechanisms.
These results may also help us improve antibody vaccines in the future, and may also help us develop precision therapies
targeting plasma cells for antibody-mediated autoimmune diseases.

Qi Hai and Wang Jianbin are the co-corresponding authors of this article; Liu Xin, assistant researcher of the School of Medicine, and Yao Jiacheng, a postdoctoral researcher at the School of Chemistry and Molecular Engineering, Peking University, are the co-first authors of this paper.
PhD student Yongshan Zhao also made important contributions
to the project.
The research was supported by grants
from the Ministry of Science and Technology, the Natural Science Foundation of China, the Joint Center for Life Sciences, the Beijing Municipal Science and Technology Commission, the Center for Frontier Research in Biostructures, the Gates Foundation, and the Howard Hughes Medical Institute.

Original link:

https://doi.
org/10.
1038/s41590-022-01345-5