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.

Keywords: B cells; CD27; CD40 ligand; CD72; immune thrombocytopenia.