Single-cell-level protein analysis revealing the roles of autoantigen-reactive B lymphocytes in autoimmune disease and the murine model

Despite antigen affinity of B cells varying from cell to cell, functional analyses of antigen-reactive B cells on individual B cells are missing due to technical difficulties. Especially in the field of autoimmune diseases, promising pathogenic B cells have not been adequately studied to date because of its rarity. In this study, functions of autoantigen-reactive B cells in autoimmune disease were analyzed at the single-cell level. Since topoisomerase I is a distinct autoantigen, we targeted systemic sclerosis as autoimmune disease. Decreased and increased affinities for topoisomerase I of topoisomerase I-reactive B cells led to anti-inflammatory and pro-inflammatory cytokine production associated with the inhibition and development of fibrosis, which is the major symptom of systemic sclerosis. Furthermore, inhibition of pro-inflammatory cytokine production and increased affinity of topoisomerase I-reactive B cells suppressed fibrosis. These results indicate that autoantigen-reactive B cells contribute to the disease manifestations in autoimmune disease through their antigen affinity.

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Cytokine Production in Mononuclear Cells of Human Milk Studied at the Single-Cell Level

Pediatric Research ◽

10.1203/00006450-199308000-00023 ◽

1993 ◽

Vol 34 (2) ◽

pp. 213-216 ◽

Cited By ~ 57

Author(s):

U Skansén-Saphir ◽

A Lindfors ◽

U Andersson

Keyword(s):

Human Milk ◽

Single Cell ◽

Mononuclear Cells ◽

Cytokine Production ◽

Single Cell Level ◽

Cell Level

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Osteoclast defects in XLA patients are negated by the lack of mature B cells and elevated inflammatory cytokine production

Bone ◽

10.1016/j.bone.2009.01.442 ◽

2009 ◽

Vol 44 ◽

pp. S139

Author(s):

L. Danks ◽

S. Workman ◽

V. Nicolaidou ◽

D. Webster ◽

B. Foxwell ◽

...

Keyword(s):

B Cells ◽

Inflammatory Cytokine ◽

Cytokine Production ◽

Inflammatory Cytokine Production

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Recombination may occur in the absence of transcription in the immunoglobulin heavy chain recombination centre

Nucleic Acids Research ◽

10.1093/nar/gkaa108 ◽

2020 ◽

Vol 48 (7) ◽

pp. 3553-3566

Author(s):

Chloé Oudinet ◽

Fatima-Zohra Braikia ◽

Audrey Dauba ◽

Ahmed Amine Khamlichi

Keyword(s):

B Cells ◽

Single Cell ◽

Chromatin Remodeling ◽

Heavy Chain ◽

Single Cell Level ◽

Mouse Line ◽

Cell Level ◽

Igh Locus ◽

Chromatin Remodeling Complexes ◽

Mechanistic Basis

Abstract Developing B cells undergo V(D)J recombination to generate a vast repertoire of Ig molecules. V(D)J recombination is initiated by the RAG1/RAG2 complex in recombination centres (RCs), where gene segments become accessible to the complex. Whether transcription is the causal factor of accessibility or whether it is a side product of other processes that generate accessibility remains a controversial issue. At the IgH locus, V(D)J recombination is controlled by Eμ enhancer, which directs the transcriptional, epigenetic and recombinational events in the IgH RC. Deletion of Eμ enhancer affects both transcription and recombination, making it difficult to conclude if Eμ controls the two processes through the same or different mechanisms. By using a mouse line carrying a CpG-rich sequence upstream of Eμ enhancer and analyzing transcription and recombination at the single-cell level, we found that recombination could occur in the RC in the absence of detectable transcription, suggesting that Eμ controls transcription and recombination through distinct mechanisms. Moreover, while the normally Eμ-dependent transcription and demethylating activities were impaired, recruitment of chromatin remodeling complexes was unaffected. RAG1 was efficiently recruited, thus compensating for the defective transcription-associated recruitment of RAG2, and providing a mechanistic basis for RAG1/RAG2 assembly to initiate V(D)J recombination.

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