IgM+ Memory B Cell Expression Predicts HIV-Associated Cryptococcosis Status

Background. The role of B cells in resistance to Cryptococcus neoformans disease (i.e., cryptococcosis) is unknown. Given evidence that IgM(+) memory B cells are required for immunity to other encapsulated pathogens, we hypothesized that these cells might contribute to resistance to cryptococcosis. Methods. We compared levels of IgM expression on memory B cells in 29 HIV-infected individuals who had a history of cryptococcosis (the HIV+CN+group) with levels in 30 human immunodeficiency virus (HIV)-infected subjects who had no history of cryptococcosis (the HIV+CN- group) and 20 HIV-uninfected subjects who had no history of cryptococcosis (the HIV- group) (cohort 1). We also determined levels of IgM expression on memory B cells in banked samples obtained before cryptococcosis onset from 31 participants in the Multicenter AIDS Cohort Study, of whom 8 had HIV infection and subsequently developed cryptococcosis (the HIV+CN+group), 8 had HIV infection and did not develop cryptococcosis (the HIV+CN- group), and 15 did not have HIV infection and did not develop cryptococcosis (the HIV- group) (cohort 2). Results. In cohort 1, the percentage of memory B cells that expressed IgM was lower among HIV+CN+ subjects, compared with HIV+CN- subjects (P < .01) and HIV- subjects (P < .05); expression of IgM on <= 50% of memory B cells was a significant predictor of C. neoformans disease status (odds ratio, 5.5; P = .03). In cohort 2, the percentage of memory B cells that expressed IgM was lower in HIV+CN+ subjects than in HIV+CN- subjects (P = .02) and HIV- subjects (P < .01); an IgM(+) memory B cell percentage of <= 38.5% was a significant predictor of future development of cryptococcosis (odds ratio, 14; P = .02). Conclusions. These findings suggest that HIV-infected persons in whom the percentage of memory B cells that express IgM is decreased might be at greater risk for the development of cryptococcosis.