The selection of mature B cells is critically dependent on the expression level of the co-receptor CD19

Abstract Background: Primary Sjögren’s syndrome (pSS) is a chronic autoimmune disease characterized by abnormal immune cell activation. This study aimed to investigate differentially expressed long non-coding RNA (lncRNA) in peripheral blood mononuclear cells (PBMCs) in patients with pSS to identify lncRNAs that affect pSS pathogenesis. Methods: Total RNA was extrated from PBMCs of 30 patients with pSS and 15 healthy persons. Transcriptome sequencing was used to screen differentially expressed lncRNAs and mRNAs in 8 RNA samples from the discovery cohort. The differentially expressed mRNAs underwent functional enrichment analysis. A protein interaction relationship (PPI) and ceRNA network was constructed. Real-time PCR was used to validate screened lncRNAs in all 45 RNA samples. Results: 1180 lncRNAs and 640 mRNAs were differentially expressed in pSS patients (fold change > 2 in healthy persons). The PPI network was constructed with 640 mRNAs and a ceRNA network with four key lncRNAs (GABPB1-AS1, PSMA3-AS1, LINC00847 and SNHG1). RT-PCR revealed that GABPB1-AS1 and PSMA3-AS1 were significantly upregulated 3.0-and 1.4-fold in the pSS group, respectively. The GABPB1-AS1 expression level was positively correlated with the percentage of B cells and IgG levels. Conclusions: GABPB1-AS1 was significently upregulated in pSS patients, and its expression level is positively correlated with the percentage of B cells and IgG levels. GABPB1-AS1 may be involved in the pathogenesis of pSS.

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Immune Cell Landscape in Gastric Cancer

BioMed Research International ◽

10.1155/2021/1930706 ◽

2021 ◽

Vol 2021 ◽

pp. 1-12

Author(s):

Yang Yang ◽

Wei He ◽

Zi-rui Wang ◽

Yu-jiao Wang ◽

Lan-lan Li ◽

...

Keyword(s):

Gastric Cancer ◽

B Cells ◽

Immune Cells ◽

Immune Cell ◽

Univariate Analysis ◽

Molecular Therapy ◽

Expression Level ◽

Regulatory Factors ◽

Normal Tissues ◽

The Relationship

Background. The tumor-infiltrating immune cells are closely associated with the prognosis of gastric cancer (GC). This article is aimed at determining the composition change of immune cells and immune regulatory factors in GC and normal tissues, depicting their prognosis value in GC, and revealing the relationship between them and GC clinical parameters. Methods. We used CIBERSORT to calculate the proportion of 22 immune cells in the GC or normal tissues; a t -test was applied to assess the expression difference of immune cells and immune regulatory factors in normal and GC tissues. The relationship of the immune cells, immune regulatory factors, and GC patients’ clinical characteristics was assessed by univariate analysis. Results. In this study, we found that the proportion of macrophages increased, while plasma cells and monocytes decreased in GC tissues. In these immune fractions, Tregs and naïve B cells were found to be correlated with GC patients’ prognosis. Interestingly, the expression of immune regulatory factors was ambiguous with their classical function in GC tissues. For example, TIM-3, FOXP3, and CMTM6 were overexpressed, while CD27 and PD-1 were underexpressed in GC tissues. We also found that IDO1, PD-1, TIGIT, and TIM-3 were highly expressed in high-grade GC tissues, the HERC2 expression level was related to patients’ gender, and the TIGIT expression level was sensitive to targeted therapy. Furthermore, our results suggested that the infiltration of Tregs and naive B cells was strongly correlated with the T stage, radiation therapy, targeted molecular therapy, and the expression levels of TIM-3 and FOXP3 in GC. Conclusion. The expression pattern of tumor-infiltrating immune cells and immune regulatory factors was systematically depicted in the GC tumor microenvironment, indicating that individualized treatment based on the tumor-infiltrating immune cells and immune regulatory factors may be beneficial to GC patients.

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Altered BCR and TLR signals promote enhanced positive selection of autoreactive transitional B cells in Wiskott-Aldrich syndrome

Journal of Experimental Medicine ◽

10.1084/jem.20150585 ◽

2015 ◽

Vol 212 (10) ◽

pp. 1663-1677 ◽

Cited By ~ 41

Author(s):

Nikita S. Kolhatkar ◽

Archana Brahmandam ◽

Christopher D. Thouvenel ◽

Shirly Becker-Herman ◽

Holly M. Jacobs ◽

...

Keyword(s):

B Cells ◽

Positive Selection ◽

B Cell ◽

Heavy Chain ◽

High Throughput Sequencing ◽

Cell Stage ◽

Wiskott Aldrich Syndrome ◽

Transitional B Cells ◽

Selection Of

Wiskott-Aldrich syndrome (WAS) is an X-linked immunodeficiency disorder frequently associated with systemic autoimmunity, including autoantibody-mediated cytopenias. WAS protein (WASp)–deficient B cells have increased B cell receptor (BCR) and Toll-like receptor (TLR) signaling, suggesting that these pathways might impact establishment of the mature, naive BCR repertoire. To directly investigate this possibility, we evaluated naive B cell specificity and composition in WASp-deficient mice and WAS subjects (n = 12). High-throughput sequencing and single-cell cloning analysis of the BCR repertoire revealed altered heavy chain usage and enrichment for low-affinity self-reactive specificities in murine marginal zone and human naive B cells. Although negative selection mechanisms including deletion, anergy, and receptor editing were relatively unperturbed, WASp-deficient transitional B cells showed enhanced proliferation in vivo mediated by antigen- and Myd88-dependent signals. Finally, using both BCR sequencing and cell surface analysis with a monoclonal antibody recognizing an intrinsically autoreactive heavy chain, we show enrichment in self-reactive cells specifically at the transitional to naive mature B cell stage in WAS subjects. Our combined data support a model wherein modest alterations in B cell–intrinsic, BCR, and TLR signals in WAS, and likely other autoimmune disorders, are sufficient to alter B cell tolerance via positive selection of self-reactive transitional B cells.

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