Circulating CXCR5+CD4+T cells assist in the survival and growth of primary diffuse large B cell lymphoma cells through interleukin 10 pathway

Diffuse large B cell lymphoma (DLBCL) is a common and aggressive cancer caused by the malignant transformation of B cells. Although it has been established that the follicular helper T (Tfh) cells play a central role in B cell development, little information is available on their involvement in DLBCL pathogenesis. We studied the role of the peripheral Tfh equivalent, the CXCR5(+) CD4(+) T cells, in DLBCL. Data showed that compared to CXCR5(-) CD4(+) T cells, CXCR5(+) CD4(+) T cells were significantly more effective at promoting the proliferation as well as inhibiting the apoptosis of primary autologous DLBCL tumor cells. Surprisingly, we found that at equal cell numbers, CXCR5(+) CD4(+) T cells in DLBCL patients secreted significantly less interleukin (IL)-21 than CXCR5(-) CD4(+) T cells, while the level of IL-10 secretion was significant elevated in the CXCR5(+) compartment compared to the CXCR5(-) compartment. Neutralization of IL-10 in the primary DLBCL-CXCR5(+) CD4(+) T cell coculture compromised the CXCR5(+) CD4(+) T cell-mediated pro-tumor effects, in a manner that was dependent on the concentration of anti-IL-10 antibodies. The CXCR5(+) compartment also contained significantly lower frequencies of cytotoxic CD4(+) T cells than the CXCR5(-) compartment. In conclusion, our investigations discovered a previously unknown pro-tumor role of CXCR5-expressing circulating CD4(+) T cells, which assisted the survival and proliferation of primary DLBCL cells through IL-10.