Abstract
We have previously shown that overexpression of BLyS/BAFF was associated with increased relative frequencies of innate “precursor” marginal zone (MZ)-like B-cells in the blood of HIV-1-infected rapid and classic progressors. However, along with relatively normal BLyS/BAFF expression levels, these cells remain unaltered in elite-controllers (EC), rather, percentages of more mature MZ-like B-cells are decreased in the blood of these individuals. Fluctuations in frequencies of blood MZ-like B-cell populations may reflect migratory patterns associated with disease progression status, suggesting an important role for these cells in HIV-1 pathogenesis. We have therefore longitudinally measured plasma levels of B-tropic chemokines by ELISA-based technology as well as their ligands by flow-cytometry on blood B-cell populations of HIV-1-infected individuals with different rates of disease progression and uninfected controls. Migration potential of B-cell populations from these individuals were determined by chemotaxis assays. We found important modulations of CXCL13-CXCR5, CXCL12-CXCR4/CXCR7, CCL20-CCR6 and CCL25-CCR9 chemokine-axes and increased cell migration patterns in HIV progressors. Interestingly, frequencies of CCR6 expressing cells were significantly elevated within the precursor MZ-like population, consistent with increased migration in response to CCL20. Although we found little modulation of chemokine-axes in EC, cell migration was greater than that observed for uninfected controls, especially for MZ-like B-cells. Overall the immune response against HIV-1 may involve recruitment of MZ-like B-cells to peripheral sites. Moreover, our findings suggest that “regulated” attraction of these cells in a preserved BLyS/BAFF non-inflammatory environment, such as encountered in EC could be beneficial to the battle and even control of HIV.
Highlights
Promising vaccine strategies as well as studies with individuals presenting natural immunity have highlighted the importance of B-cells in the immune response against HIV [1]
3 P = 0.0008 and 0.001 and 0.02 nadir CD4 for the comparison between rapid and classic progressors, rapid and viremic slow progressors, and rapid and aviremic slow progressors, respectively, as determined by the Mann-Whitney test. 4 50 copies/ml corresponds to the detection threshold of the viral load test
We found the greatest modulation of the CCR6-CCL20 axis in rapid and classic progressors, which is consistent with active cellular recruitment towards peripheral and mucosal sites
Summary
Promising vaccine strategies as well as studies with individuals presenting natural immunity have highlighted the importance of B-cells in the immune response against HIV [1]. Despite a reduction in total B-cells, we have observed augmented frequencies of a population presenting features shared by both transitional immature (TI) and innate marginal zone (MZ) B-cells, designated as “precursor” MZ-like, in the blood of HIV-1-infected rapid and classic progressors [6,7]. These were concomitant with high levels of BLyS/BAFF in plasma and on the surface of blood mDCs in these individuals, as soon as in the acute phase and persisted throughout infection despite highly active therapy. These findings are in line with growing evidence suggesting that innate B-cell responses are involved in the fight against HIV [8]
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call