The impact of active HIV-1 replication on the physiological age-related decline of immature-transitional B-cells in HIV-1 infected children.

Objective: To characterize the level of immature-transitional B-cells in blood during pediatric HIV-1 infection in relation to active or suppressed viremia. We also aimed at characterizing the level of expression of CXCR4, CXCR5 and CCR7 on immature-transitional B-cells, as these receptors are important mediators for homing of B-cells. Design: Forty-eight HIV-1 vertically infected children (33 viral controllers and 15 viremic patients) and 33 age-matched healthy controls were enrolled in a cross-sectional study. Methods: We measured the levels of peripheral immature-transitional B-cells in all groups in relation to switched memory B-cells by flow cytometry. In parallel we evaluated CXCR4, CXCR5 and CCR7 expression on immature-transitional B-cells and measured plasma levels of CXCL12, BAFF and interleukin-7 by ELISA. Results: We observed a lack of physiological age-related decline of immature-transitional B-cells in viremic children in parallel to a decreased level of switched memory B-cells. Interestingly, immature-transitional B-cells from viremic children presented with high levels of CXCR4. On the contrary, the level of CXCL12, the natural ligand for CXCR4, was lowest in the HIV-1 infected group, as compared with controls. Conclusion: Control of HIV-1 viremia through antiretroviral treatment appears to be crucial in decreasing the expansion and alteration of immature-transitional B-cells.