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Nature Sub-Journal: After recovering, still immunodeficiency, what does the new coronavirus do to B cells?

 Last Update: 2021-09-29
 Source: Internet
 Author: User

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At the end of 2019, a new type of coronavirus (SARS-CoV-2) was confirmed as the pathogen of severe acute respiratory infection of COVID-19 .

The clinical manifestations of patients with SARS-CoV-2 infection vary widely, ranging from asymptomatic to life-threatening severe illness, including acute respiratory distress syndrome (ARDS)
.

The so-called "cytokine storm", that is, the uncontrollable activation of the inflammatory response, significantly promotes the occurrence of ARDS

At the end of 2019, a new type of coronavirus (SARS-CoV-2) was confirmed as the pathogen of severe acute respiratory infection of COVID-19 .

This study aims to evaluate the signal characteristics of B cells in COVID-19 patients, and to determine how changes in the abundance of specific metabolites affect B cell receptor signals by analyzing the serum metabolic components obtained from COVID-19 patients
.

SARS-CoV-2 infection changes the immune phenotype and B cell function of recovered patients

Specific B cell subsets play a key role in antiviral humoral immunity

To detect the response of B cells to bcr-dependent signals, we used F(ab')2 anti-human Ig(M + G) antibody to stimulate B cells for 24 hours

2.
SARS-CoV-2 infection changes the BCR signal and b-cell metabolism of recovered patients

CD19 is a key regulator of BCR signal transduction, b cell development and humoral immune response
.

Compared with the healthy control group, the levels of total CD19, phosphorylated CD19 and phosphorylated Btk in the patient's B cells were significantly reduced (Figure 2a )

CD19 is a key regulator of BCR signal transduction, b cell development and humoral immune response

In order to evaluate the redox status of B cells in COVID-19 patients, we used F(ab')2 anti-human Ig(M + G) to stimulate the B cells of patients and healthy controls to determine the total ROS production

3.
SARS-CoV-2 infection changes the serum metabolite profile and transcriptome profile of B cells

SARS-CoV-2 infection changes the serum metabolite profile and transcriptome profile of B cells

The levels of l-arginine, l-glutamic acid, l-isoleucine, l-cystine and l-cysteine in the serum of recovered patients with new coronary pneumonia were significantly reduced
.

Compared with healthy controls, the levels of glutamate and cysteine in the serum of recovered COVID-19 patients were significantly lower

The levels of l-arginine, l-glutamic acid, l-isoleucine, l-cystine and l-cysteine in the serum of recovered patients with new coronary pneumonia were significantly reduced

4.
SARS-CoV-2 infection changes the BCR signaling pathway by affecting the early activation of B cells

SARS-CoV-2 infection changes the BCR signaling pathway by affecting the early activation of B cells

In terms of B cell proliferation, compared with the original B cells and memory B cells of the healthy control group, the contact area of the patient's initial B cells was reduced when activated for 3 minutes, and the contact area of the patient's memory B cells was significantly reduced when activated for 5 minutes (Figure 4a-c )
.
For the total BCR signal, compared with the uninfected B cells and memory B cells of the healthy control group, the MFI of pY of the patients' uninfected B cells and memory B cells was significantly reduced at 3 and 5 minutes (Figure 4a, B, d)
.
Compared with the naive B cells and memory B cells of the healthy control group, the MFI of BCRs was significantly reduced at 3 and 5 minutes (Figure 5a-c)
.

In addition, compared with the uninfected B cells and memory B cells of the healthy control group, the MFI of pSHIP was significantly reduced 5 minutes after activation of uninfected B cells and memory B cells (Figure 5a, B, d)
.
Regarding the activation of CD19, the MFI of pCD19 in uninfected B cells and memory B cells of patients was significantly reduced at 3 and 5 minutes compared with uninfected B cells and memory B cells in the healthy control group (Figure 6a-c)
.
These results indicate that SARS-CoV-2 infection alters the BCR signaling pathway by inhibiting the early activation of naive B cells and memory B cells
.

Through transcriptome and metabolism studies, this study found that the expression of genes related to metabolism and metabolites was unregulated, and B cell ROS increased in rehabilitation patients, indicating that B cell metabolism in rehabilitation patients increased
.
Interestingly, the use of antioxidants can partially rescue CD19 expression in recovered patients
.

In addition, we found that the expression of CD19 in the spleen of SARS-CoV-2 mice was also reduced, or it can be considered that the expression of CD19 may also be reduced in infected patients
.
It is worthy of attention to detect the expression of CD19 and the metabolic status of B cells in patients with mild and severe infections
.
In addition, the correlation between the expression of CD19 and the different metabolic states of B cells is worth studying
.
Even more exciting is that correcting the increased ROS in B cells rescued the expression of CD19 and BCR signaling, which may correct the immune status of recovered patients
.
It is not clear whether recovered patients with reduced CD19 expression are more likely to be re-infected with SARS-CoV-2.
If this is true, metabolic regulators such as NAC have the potential to clinically prevent secondary infections in recovered patients
.
Although it was found that the expression of CD19 was reduced, there was no change in the level of CD19 mRNA in the B cells of recovered patients, indicating that SARS-CoV-2 infection may reduce the level of CD19 expression during the post-transcriptional translation period
.
We also detected several molecules in the BCR signaling pathway from RNA-Seq, but did not find differences in CD19 mRNA and molecules in the BCR signaling pathway between healthy controls and patients
.
This may be the reason why the BCR signaling pathway does not appear in the KEGG-enriched signaling pathway
.

In addition, we found that the expression of CD19 in the spleen of SARS-CoV-2 mice was also reduced, or it can be considered that the expression of CD19 may also be reduced in infected patients
.
It is worthy of attention to detect the expression of CD19 and the metabolic status of B cells in patients with mild and severe infections
.
In addition, the correlation between the expression of CD19 and the different metabolic states of B cells is worth studying
.
Even more exciting is that correcting the increased ROS in B cells rescued the expression of CD19 and BCR signaling, which may correct the immune status of recovered patients
.
It is not clear whether recovered patients with reduced CD19 expression are more likely to be re-infected with SARS-CoV-2.
If this is true, metabolic regulators such as NAC have the potential to clinically prevent secondary infections in recovered patients
.
Prevention Although it was found that the expression of CD19 was reduced, there was no change in the level of CD19 mRNA in the B cells of recovered patients, indicating that SARS-CoV-2 infection may reduce the level of CD19 expression during the post-transcriptional translation period
.
We also detected several molecules in the BCR signaling pathway from RNA-Seq, but did not find differences in CD19 mRNA and molecules in the BCR signaling pathway between healthy controls and patients
.
This may be the reason why the BCR signaling pathway does not appear in the KEGG-enriched signaling pathway
.

Bacterial and fungal infections are common complications in patients with viral pneumonia and lead to increased mortality
.
Analyzing the signal characteristics of B cells in patients with COVID-19 helps to assess whether COVID-19 infection will make patients more susceptible to other diseases, and to better understand how abnormal metabolism in the patient’s serum affects B cell signals, which may inspire targeting Development of new therapeutic strategies for specific metabolic pathways
.
Different compounds that alter cell metabolism and redox status are currently being tested in preclinical and clinical studies for the treatment of autoimmune diseases, and may also be used to suppress overactive immune responses during viral infections
.

Original source:

Jing et al.
SARS-CoV-2 infection causes immunodeficiency in recovered patients by downregulating CD19 expression in B cells via enhancing B-cell metabolism.

Signal Transduction and Targeted Therapy (2021) 6:345; https://doi.
org/10.
1038/s41392-021-00749-3

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