HIV-1 induces phenotypic and functional perturbations of B cells in chronically infected individuals

A number of perturbations of B cells has been described in the setting of H IV infection; however, most remain poorly understood. To directly address t he effect of HIV replication on B cell function, we investigated the capaci ty of B cells isolated from HIV-infected patients to respond to a variety o f stimuli before and after reduction of viremia by effective antiretroviral therapy. B cells taken from patients with high levels of plasma viremia we re defective in their proliferative responses to various stimuli. Viremia w as also associated with the appearance of a subpopulation of B cells that e xpressed reduced levels of CD21. After fractionation into CD21(high)- and C D21(low)-expressing B cells, the CD21(low) fraction showed dramatically red uced proliferation in response to B cell stimuli and enhanced secretion of immunoglobulins when compared with the CD21(high) fraction. Electron micros copic analysis of each fraction revealed cells with plasmacytoid features i n the CD21(low) B cell population but not in the CD21(high) fraction. These results indicate that HIV viremia induces the appearance of a subset of B cells whose function is impaired and which may be responsible for the hyper gammaglobulinemia associated with HIV disease.