CD72 is a coreceptor of BCR, which has a conserved intracellular domain containing an immunoreceptor tyrosine-based inhibitory motif (ITIM) [23]. CD72 negatively regulates BCR signalling by recruiting Src homology 2 domain-containing protein tyrosine phosphatase-1 (SHP-1) at the ITIM [17, 24]. Variations in CD72 gene have been reported in immunological diseases. For example, CD72 regulates the development of systemic lupus erythematosus (SLE), a prototype systemic autoimmune disease characterised by autoantibody production. Consistently CD72 expression on B cells was reported to be decreased in patients with SLE and multiple sclerosis compared to healthy controls [25, 26], suggesting that a decrease in CD72 expression has several immune consequences, including negative effects on BCR signalling and immune responses.
According to our results, althoughCD72 expression on B cells did not change significantly, it was significantly lower on CD5 + B cells of patients with HBV infection than on those of healthy donors. In contrast, CD72 expression was significantly higher on CD5 − B cells of patients with HBV infection than on those of healthy donors. Since CD72 inhibits BCR activation, decreased CD72 expression on CD5 + B cells may reduce negative regulation through CD72. In other words, this downregulation may have directly increasedCD5 + B cell activation. Furthermore, our analysis revealed that CD72 expression was negatively correlated with CD5 + expression on B cells. Using a BrdU assay, we demonstrated that CD72 has an important effect on CD5 + B cell proliferation. This implied that CD72 expression influenced the ratio of CD5 + B cells. When CD72 suppression was accompanied with F(ab’)2 anti-human IgM stimulation, proliferation of CD5 + B cells increased significantly, whereas CD5 − B cells were tolerant to this cha nge. Therefore, it seems that CD5 + and CD5 − B cells respond differently to variations in CD72 expression, which is worthy of further exploration.
Activation of signalling pathways was investigated in B cells with and without CD72 suppression. ERK and Syk signalling were found to be affected by CD72 suppression. Both ERK and Syk signalling inhibitors suppressedCD72-related CD5 + B cell proliferation, indicating that CD72 influences CD5 + B cell proliferation through Syk and ERK signalling. Taken together, our results indicate that HBV infection causes differential CD72 expression onCD5 + and CD5 − B cells.CD72 downregulation promotes proliferation of CD5 + B cells through ERK and Syk signalling. Since CD5 is involved in B cell differentiation and immune regulation, changes in CD72 expression on CD5 + B cells may closely influence the immune responses of B cells.
Meanwhile, it seems that decrease in CD72 expression induces several immune responses, including negative effects on BCR and immune responses. However, in HBV infection, decreased CD72 expression on CD5 + B cells may have caused IL-10 secretion, which may consequently contribute to immune suppression.
In conclusion, decreased CD72 expression may induce the proliferation of CD5 + B cells, thereby causing a downward trend of CD72 on total CD5 + B cells. Taking the predominant status of IL-10 secretion [19, 20], increased CD5 + B cells with reduced CD72 expression may result in increased IL-10 expression, imparting a certain inhibitory effect on anti-HBV responses.