CD34⁺CD10⁺CD19^- Cells in Patients with Unhealthy Alcohol Use Stimulate the M2b Monocyte Polarization

M2b monocytes commonly isolated from patients with unhealthy alcohol use (Alc) have been described as cells that make the host susceptible to opportunistic infections. CD34⁺CD10⁺CD19^- cells are multilineage progenitors of CD19⁺ cells, and we show that the effect of these cells from the peripheral blood on M2b monocyte polarization differed between healthy donors and Alc in this study. In healthy donors, these cells consistently differentiated into high-mobility group box-1 (HMGB1)-nonproducing cells (CD19⁺ cells) in response to retinoic acid (RA). However, owing to the lack of expression of RA receptor (RAR), these cells from Alc failed to differentiate into CD19⁺ cells under the same RA stimulation. Conditioned medium (CM) of these cells from Alc induced the polarization of M2b monocytes, which increases the susceptibility of hosts to opportunistic infections in Alc. When the alcoholic individuals were subjected to 2 weeks of abstinence from alcohol, these cells from Alc recovered their RAR expression and differentiated into CD19⁺ cells. Moreover, the CM of these cells from Alc after abstinence lost its ability to induce M2b monocyte polarization. These results indicate that these cells from Alc have different properties from those of healthy donors. In Alc, these cells without RAR stimulate M2b monocyte polarization through the production of HMGB1.