Viral load determines the B-cell response in the cerebrospinal fluid during human immunodeficiency virus infection

Abstract

Objective Human immunodeficiency virus (HIV) infection of the central nervous system (CNS) is frequently associated with intrathecal immunoglobulin synthesis and cerebrospinal fluid (CSF) pleocytosis, but little is known about the B‐cell response in the CSF of these patients. In this study, we investigated the relation between virus load and the frequency and phenotype of B cells in the CSF of HIV‐infected patients. Methods The distribution of T cells, B cells, short‐lived plasmablasts, and long‐lived plasma cells was analyzed by flow cytometry in CSF and peripheral blood of 33 patients with HIV infection compared with 12 patients with noninfectious CNS diseases. HIV RNA copy number in CSF and serum was quantified by kinetic polymerase chain reaction. Results B‐cell and plasmablast levels were increased in the CSF of HIV‐infected patients compared with patients with noninfectious CNS diseases. Whereas CSF B cells were found at similar frequency during early and late stages of HIV infection, plasmablasts were more prevalent in the CSF during early infection. Plasmablasts in the CSF correlated with intrathecal IgG synthesis and even stronger with HIV RNA copy numbers in CSF, in particular, in untreated, early HIV‐infected individuals. Initiation of antiviral treatment in therapy‐naive patients strongly decreased HIV copy numbers and plasmablasts in CSF. Interpretation Our findings demonstrate that HIV infection of the CNS triggers an early profound B‐cell response, with plasmablasts serving as the main virus‐related B‐cell subset in the CSF. Ann Neurol 2007