B cell responses in HIV infection of the central nervous system

Background and Aim: Central nervous system (CNS) involvement is common in human immunodeficiency virus (HIV) infection. HIV-1 is a neurotropic virus which may early during the course of infection invade the CNS. As the CNS constitutes an immunologically protected compartment, neurological progression is possibly independent of systemic viral burden. Little is still known about the role of the immune system in controlling HIV infection in the brain. Although HIV infection of the CNS is frequently associated with intrathecal immunoglobulin (Ig) synthesis, and high Ig titers have been observed in the CSF, particularily in early HIV infected patients, the nature of the B cell response and the role of antibodies in CNS HIV infection has so far received little attention. In this study, we analyzed the frequency and phenotype of B cells in the CSF in relation to HIV infection. Methods: We examined the CSF and blood of 33 HIV infected patients in different stages of disease and a control group of patients with other neurological diseases. CSF white cell count was determined and CSF checked for occurrence of oligoclonal bands. In CSF and serum, total protein, albumin, and Ig levels were detected by nephelometry. In HIV positive patients, HIV RNA levels were measured in CSF and plasma. Using four-colour flow cytometry, we analyzed the CSF immune cell repertoire, paying particular attention to different B cell subsets. Results and discussion: B cells and plasmablasts but not plasma cells or T cells were elevated in the CSF of HIV infected patients compared to patients with other neurological diseases. In blood, however, these lymphocyte subsets were not differently expressed between HIV and control patients. While CSF B cells were found at a similar frequency during all stages of HIV infection, short-lived plasmablasts were more frequently found in the CSF of asymptomatic HIV infected patients receiving no antiretroviral therapy. HIV RNA levels in blood and CSF correlated with the extent of plasmablast recruitment. In CSF, plasmablasts were associated with intrathecal antibody production which was also strongly linked to viral burden in CSF. Our findings demonstrate that presence of HIV in the CSF leads to a profound early B cell response with plasmablasts being the main anti-viral effector B cell subset in the CNS. Our findings suggest a role of HIV in the control of infection in particular during the early phase of disease.