Upregulation of CD72 expression on CD19⁺CD27⁺ memory B cells by CD40L in primary immune thrombocytopenia

Abstract

CD72 is a co-receptor of B cells and regulates B cell activation. Although aberrant expression of CD72 has been reported in primary immune thrombocytopenia (ITP), it is uncertain whether this aberrant expression is restricted to specific B cell subsets. Furthermore, the mechanisms that regulate CD72 expression are unknown. In this study, we found higher frequency of CD19 B cells, CD19 CD27 memory B cells and lower frequency of CD19 CD27 naive B cells in active ITP patients compared with controls and patients in remission. CD72 expression on CD19 CD27 cells was upregulated in active ITP patients and correlated with platelet count and anti-platelet autoantibodies. In vitro, CD40L could specifically induce CD72 upregulation on CD19 CD27 B cells. In combination with CD40L, interleukin (IL) 10 and BAFF (also termed TNFSF13B) further enhanced CD72 expression on CD19 CD27 B cells, whereas IL21 reduced CD72 upregulation. CD72mRNA expression after CD40L stimulation was increased in ITP patients and controls. Significant increase of CD40L on CD4 T cells was correlated with CD72 expression on CD19 CD27 B cells in ITP patients. In conclusion, upregulation of CD72 expression on CD27 memory B cells might take part in the pathogenesis of ITP. Elevated CD40L on CD4 cells combined with cytokines might contribute to the upregulation of CD72 expression on CD27 memory B cells.

Assessment on the lung injury of mice posed by airborne PM2.5 collected from developing area in China and associated molecular mechanisms: from histopathology to integrated transcriptome analysis

“…The overexpression of Cd72 found in this work from PM 2.5 -exposed group may promote B cell survival and proliferation, and enhance release of CD23, and then activate the immune response [37][38][39]. In addition, anti-CD72 monoclonal antibodies (mAbs) can activate CD19 tyrosine phosphorylation [40]. The similar result was observed in this work (the up-regulation of Cd19 induced by PM 2.5 ).…”

Differential gene expression in chicken primary B cells infected ex vivo with attenuated and very virulent strains of infectious bursal disease virus (IBDV)

“…There are three known receptors for BAFF that are expressed on B cells in varying amounts related to the maturation of the cell, and BAFF-induced signalling stimulates B cells to undergo proliferation and counters apoptosis [42]. CD72 is a co-receptor on B cells, the expression of which is enhanced by BAFF [43]. It contains two immunoreceptor tyrosine-based inhibitory motifs (ITIMs), ITIM1 and ITIM2, and studies have associated it with both positive and negative signalling [44].…”

A regulatory role for CD72 expression on B cells and increased soluble CD72 in primary Sjogren’s syndrome

“…The involvement of B lymphocytes has been increasingly recognized in the occurrence of primary Sjogren's Syndrome (pSS) [6]. And CD72, being a coreceptor of B cell receptor (BCR), has been reported to be an important regulator in the pathogenesis of several autoimmune diseases [20][21][22][23]25]. However, the role of CD72 in pSS has been rarely studied [24].…”

“…In multiple sclerosis, the expression of CD72 decreased along with an increase in expression of its ligand CD100 on T cells and abnormal levels of several inflammatory factors [22,23]. Conversely, CD72 expression was upregulated on CD19 + CD27+ memory B cells in immune thrombocytopenia (ITP), and was associated with platelet count and anti-platelet antibodies [25]. As a negative regulator of BCR signals, once B cells are stimulated by antigens, CD72 molecules would be recruited by BCR signals to the kinase-rich BCR complex and be phosphorylated.…”