The diversity of the plasmablast signature across species and experimental conditions: A meta‐analysis

Abstract

Antibody‐secreting cells (ASC) are divided into two principal subsets, including the long‐lived plasma cell (PC) subset residing in the bone marrow and the short‐lived subset, also called plasmablast (PB). PB are described as a proliferating subset circulating through the blood and ending its differentiation in tissues. Due to their inherent heterogeneity, the molecular signature of PB is not fully established. The purpose of this study was to decipher a specific PB signature in humans and mice through a comprehensive meta‐analysis of different data sets exploring the PB differentiation in both species and across different experimental conditions. The present study used recent analyses using whole RNA sequencing in prdm1‐GFP transgenic mice to define a reliable and accurate PB signature. Next, we performed similar analysis using current data sets obtained from human PB and PC. The PB‐specific signature is composed of 155 and 113 genes in mouse and human being, respectively. Although only nine genes are shared between the human and mice PB signature, the loss of B‐cell identity such as the down‐regulation of PAX5, MS4A1, (CD20) CD22 and IL‐4R is a conserved feature across species and across the different experimental conditions. Additionally, we observed that the IRF8 and IRF4 transcription factors have a specific dynamic range of expression in human PB. We thus demonstrated that IRF4/IRF8 intranuclear staining was useful to define PB in vivo and in vitro and able to discriminate between atypical PB populations and transient states.

Molecular Mechanisms Driving IL-10- Producing B Cells Functions: STAT3 and c-MAF as Underestimated Central Key Regulators?

“…Moreover, BHLHE40 is overexpressed in anergic CD21 low B cells of patients with hepatitis C virus, a subset recently underlined as pathogenic in autoimmune diseases. The role of BHLHE40 in controlling Breg expansion has to be determined and interestingly, we recently underlined that BHLHE40 is a common factor downregulated during the PB differentiation ( 67 ).…”

“…The Blimp-1 regulated genes have been extensively studied during the B-cell differentiation, revealing that Blimp1 could act as both transcriptional repressor and activator. Using streptavidin-mediated chromatin precipitation coupled with deep sequencing (Bio-ChIP), the Il10 gene was robustly identified among the 93 genes potentially directly activated by Blimp-1 ( 66 , 67 ). Regulatory plasma cells producing IL-10 have been reported in mice in EAE and during the Salmonella Typhimurium infection ( 3 , 4 ) In EAE, the PB (CD138 + CD44 high ) subset was the main IL-10 producer population, generated through a germinal center (GC) independent pathway as the EAE course remained unchanged in Bcl6 yfp/yfp knock-out mice.…”

Gene expression profiling reveals B cells are highly educated by the pancreatic environment during autoimmune diabetes

“…2A, ESM Table 2). Other differentially expressed genes, such as Tmem176a and Tmem176b , are expressed both in plasma cells [28] and in innate lymphoid cell types [29]. Considering this, we compared the set of upregulated genes found in CD19 - CD138 + cells from both PLN and pancreatic islets, with published ASC signature genes [22] and found 84 shared genes in the PLN, and 89 shared genes in the pancreatic islets (Venn diagrams, Fig.…”

“…These results imply that islet-specific CD19 + B cells upregulate genes associated with antibody secretion but are not actively engaged in secreting immunoglobulins. Based only on gene expression profiles, it is difficult to discern whether pancreatic CD19 + B cells are at the stage of pre-plasmablasts or whether they may still be precursors, as many genes in this pathway are transitional or are expressed continuously [28]. Functional assays and assessment of protein expression using CD19 + B cells from both the lymph node and pancreas may provide more definitive evidence.…”

Gene expression profiling in NOD mice reveals that B cells are highly educated by the pancreatic environment during autoimmune diabetes

“…2 a, ESM Tables 2 and 3 ). Other DEGs, including Tmem176a and Tmem176b , are expressed both in plasma cells [ 26 ] and in innate lymphoid cells [ 27 ]. Upregulated genes in CD19 – CD138 + cells from both tissues were compared with ASC signature genes [ 21 ], with shared genes found in both tissues (Fig.…”