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Editor’s note iNature is China’s largest academic official account.
It is jointly created by the doctoral team of Tsinghua University, Harvard University, Chinese Academy of Sciences and other units.
The iNature Talent Official Account is now launched, focusing on talent recruitment, academic progress, scientific research information, interested parties can Long press or scan the QR code below to follow us
.
iNature self-reactive B-cell progenitor cells are cleared through the central tolerance checkpoint, a process that is thought to be limited to mammalian bone marrow
.
On October 8, 2021, the joint communication between Heping Xu and Danyang He of West Lake University published a research paper entitled "Early developing B cells undergo negative selection by central nervous system-specific antigens in the meninges" in Immunity.
Continuous trajectories of B cell development in the meninges of mice and non-human primates
.
Meningeal B cells are mainly located in the dural sinus, where endothelial cells express the necessary niche factors that support the development of B cells
.
Conjoined symbiosis experiments and lineage tracing show that B cells in meningeal development are constantly replenished from progenitor cells derived from hematopoietic stem cells (HSC) through a circulation-independent approach
.
Autoreactive immature B cells that recognize myelin oligodendrocyte glycoprotein (MOG), a central nervous system-specific antigen, are specifically cleared from the meninges
.
In addition, the genetic deletion of the Mog gene restores the self-reactive B cell population in the meninges
.
These findings identify the meninges as a unique reservoir for B cell development, allowing negative selection in situ to ensure a local non-self-reactive immune repertoire
.
Random V(D)J recombination of immunoglobulin (Ig) loci usually produces autoreactive B cells expressing self-recognizing B-cell receptors (BCR), which are tolerated through autoantigen-dependent central and peripheral Checkpoints are eliminated or inactivated to prevent autoimmune reactions
.
However, when the local concentration of highly tissue-specific self-antigens such as myelin oligodendrocyte glycoprotein (MOG), a glycoprotein that is only expressed in the central nervous system (CNS), is insufficient, in order to Negative selection is initiated in the bone marrow (BM) and spleen, and autoreactive B cells can escape these tolerance checkpoints and persist in the mature B cell pool
.
For a long time, the brain has been regarded as an immune-exempt organ.
Due to the lack of lymphatic drainage and the inaccessibility of immune cells, it is unable to initiate an effective immune response
.
However, this traditional concept has been modified due to the (re)discovery of meningeal lymphatic vessels under steady-state conditions
.
Meninges has become an active neuroimmune interface, which contains a large number of immune cells that mediate meningeal immunity and participate in different neuroinflammatory conditions, including neurophilic infections and multiple sclerosis
.
Single-cell analysis studies have shown that B cells are present in the meninges of mice
.
Recent work has also shown that the meninges contain immature and mature B cells
.
Despite these advances, the contribution of these B cells to meningeal immunity and immune homeostasis of the central nervous system is largely unknown
.
In particular, self-reactive immature and mature B cells recognize central nervous system-specific antigens, which escape the tolerance checkpoints in the BM and spleen, and may also be present in the meninges
.
Therefore, whether and how autoreactive B cells respond to CNS-specific antigens in the meninges remains to be elucidated
.
Schematic diagram of the summary of meningeal B lymphocyte development and negative screening studies (picture from Immunity) This study uses massively parallel single-cell RNA sequencing (scRNA-seq) analysis to reveal the continuous trajectory of mouse meningeal development B cells (from primitive to immature) B cells), which is confirmed by two recent studies
.
The same B cell development trajectory was also found in the meninges of non-human primates (NHP)
.
The lineage tracing of hematopoietic stem cells (HSC) shows that the developing B cells of the meninges are constantly being replenished from HSC-derived progenitor cells
.
The Parabiotic mouse model further proves that the replenishment of B cells in meningeal development has nothing to do with circulation
.
MOG protein is present in the meninges, but not in the skull, tibia, femur, or spleen
.
Importantly, immature B cells that recognize MOG are specifically eliminated in the meninges of IgHMOG knock-in mice (also called Th mice)
.
Consistent with these results, the deletion of the Mog gene restored the self-reactive B cell population in the meninges
.
In summary, the data from this study shows that the meninges serve as a unique reservoir for B cell development, allowing in situ negative selection of CNS antigen autoreactive B cells as an additional checkpoint layer to strictly maintain local non-self-reactivity Immune to the microenvironment
.
Researchers Xu Heping and He Danyang of West Lake University are the co-corresponding authors of the paper.
Doctoral students Wang Yan and Chen Tianyu of West Lake University and research assistant Xu De are the co-first authors of this paper
.
This project is funded by the Key Research and Development Program of the Ministry of Science and Technology, the National Natural Science Foundation of China, the West Lake Laboratory, and the West Lake Education Foundation; the implementation of the project was supported by the Experimental Animal Center, streaming platform, genomics platform and supercomputing platform of West Lake University.
Support
.
Original link: https://
It is jointly created by the doctoral team of Tsinghua University, Harvard University, Chinese Academy of Sciences and other units.
The iNature Talent Official Account is now launched, focusing on talent recruitment, academic progress, scientific research information, interested parties can Long press or scan the QR code below to follow us
.
iNature self-reactive B-cell progenitor cells are cleared through the central tolerance checkpoint, a process that is thought to be limited to mammalian bone marrow
.
On October 8, 2021, the joint communication between Heping Xu and Danyang He of West Lake University published a research paper entitled "Early developing B cells undergo negative selection by central nervous system-specific antigens in the meninges" in Immunity.
Continuous trajectories of B cell development in the meninges of mice and non-human primates
.
Meningeal B cells are mainly located in the dural sinus, where endothelial cells express the necessary niche factors that support the development of B cells
.
Conjoined symbiosis experiments and lineage tracing show that B cells in meningeal development are constantly replenished from progenitor cells derived from hematopoietic stem cells (HSC) through a circulation-independent approach
.
Autoreactive immature B cells that recognize myelin oligodendrocyte glycoprotein (MOG), a central nervous system-specific antigen, are specifically cleared from the meninges
.
In addition, the genetic deletion of the Mog gene restores the self-reactive B cell population in the meninges
.
These findings identify the meninges as a unique reservoir for B cell development, allowing negative selection in situ to ensure a local non-self-reactive immune repertoire
.
Random V(D)J recombination of immunoglobulin (Ig) loci usually produces autoreactive B cells expressing self-recognizing B-cell receptors (BCR), which are tolerated through autoantigen-dependent central and peripheral Checkpoints are eliminated or inactivated to prevent autoimmune reactions
.
However, when the local concentration of highly tissue-specific self-antigens such as myelin oligodendrocyte glycoprotein (MOG), a glycoprotein that is only expressed in the central nervous system (CNS), is insufficient, in order to Negative selection is initiated in the bone marrow (BM) and spleen, and autoreactive B cells can escape these tolerance checkpoints and persist in the mature B cell pool
.
For a long time, the brain has been regarded as an immune-exempt organ.
Due to the lack of lymphatic drainage and the inaccessibility of immune cells, it is unable to initiate an effective immune response
.
However, this traditional concept has been modified due to the (re)discovery of meningeal lymphatic vessels under steady-state conditions
.
Meninges has become an active neuroimmune interface, which contains a large number of immune cells that mediate meningeal immunity and participate in different neuroinflammatory conditions, including neurophilic infections and multiple sclerosis
.
Single-cell analysis studies have shown that B cells are present in the meninges of mice
.
Recent work has also shown that the meninges contain immature and mature B cells
.
Despite these advances, the contribution of these B cells to meningeal immunity and immune homeostasis of the central nervous system is largely unknown
.
In particular, self-reactive immature and mature B cells recognize central nervous system-specific antigens, which escape the tolerance checkpoints in the BM and spleen, and may also be present in the meninges
.
Therefore, whether and how autoreactive B cells respond to CNS-specific antigens in the meninges remains to be elucidated
.
Schematic diagram of the summary of meningeal B lymphocyte development and negative screening studies (picture from Immunity) This study uses massively parallel single-cell RNA sequencing (scRNA-seq) analysis to reveal the continuous trajectory of mouse meningeal development B cells (from primitive to immature) B cells), which is confirmed by two recent studies
.
The same B cell development trajectory was also found in the meninges of non-human primates (NHP)
.
The lineage tracing of hematopoietic stem cells (HSC) shows that the developing B cells of the meninges are constantly being replenished from HSC-derived progenitor cells
.
The Parabiotic mouse model further proves that the replenishment of B cells in meningeal development has nothing to do with circulation
.
MOG protein is present in the meninges, but not in the skull, tibia, femur, or spleen
.
Importantly, immature B cells that recognize MOG are specifically eliminated in the meninges of IgHMOG knock-in mice (also called Th mice)
.
Consistent with these results, the deletion of the Mog gene restored the self-reactive B cell population in the meninges
.
In summary, the data from this study shows that the meninges serve as a unique reservoir for B cell development, allowing in situ negative selection of CNS antigen autoreactive B cells as an additional checkpoint layer to strictly maintain local non-self-reactivity Immune to the microenvironment
.
Researchers Xu Heping and He Danyang of West Lake University are the co-corresponding authors of the paper.
Doctoral students Wang Yan and Chen Tianyu of West Lake University and research assistant Xu De are the co-first authors of this paper
.
This project is funded by the Key Research and Development Program of the Ministry of Science and Technology, the National Natural Science Foundation of China, the West Lake Laboratory, and the West Lake Education Foundation; the implementation of the project was supported by the Experimental Animal Center, streaming platform, genomics platform and supercomputing platform of West Lake University.
Support
.
Original link: https://
