Circulating memory B-cell subpopulations are affected differently by HIV infection and antiretroviral therapy

Objective: To determine if the depletion of IgM memory B cells might contribute to the increased susceptibility of HIV patients to pneumococcal infection, memory B-cell subpopulations were investigated in HIV patients, including patients receiving antiretroviral therapy (ART). Methods: Blood B cells with the phenotype of IgM memory B cells (CD27(+), IgM(+)) and switched memory B cells (CD27(+), IgM(-)) were measured in antiretroviral-treated (n=32) and untreated (n=24) HIV patients and non-HIV controls (n=35). Serum levels of IgG and IgG2 antibodies to pneumococcal polysaccharides, IgG, IgG subclasses, IgM and IgA were also assayed in HIV patients. Results: Switched memory B-cell counts were lower than controls in HIV patients (P < 0.01) irrespective of antiretroviral status and correlated with CD4 T-cell counts (r=0.56, P=0.001) in treated patients. In untreated patients, IgM memory B-cell counts correlated with CD4 T-cell counts (r=0.73, P < 0.0001) reflecting higher values than controls in patients with CD4 T-cell counts greater than 300 cells/mu l (P=0.004) and lower values than controls in patients with CD4 T-cell counts below 300 cells/mu l (P=0.0001). There was no relationship between serum levels of pneumococcal antibodies and IgM or switched memory B cells. Conclusion: The depletion of IgM memory B cells in untreated HIV patients with a CD4 T-cell count below 300 cells/mu l might be a risk factor for pneumococcal infection. The depletion of switched memory B cells is a complication of HIV infection irrespective of ART and might contribute to impaired IgG antibody responses. Memory B-cell subpopulations might predict the risk of pneumococcal sepsis more accurately than the CD4 T-cell count or pneumococcal antibody levels. (c) 2007 Lippincott Williams & Wilkins.