E-033. Host Resistance to Cryptococcus neoformans: Exploring the Role of the IgM Memory B-cell Compartment

K. Subramaniam1, A. Guh2, L. Hanau2, B. Metzger2, L-A. Pirofski1;
1Albert Einstein Coll. of Med., Bronx, NY, 2Montefiore Med. Ctr., Bronx, NY.

The role of cell-mediated immunity in host defense against Cryptococcus neoformans (CN) has been well documented; however, the role of B-cells still requires elucidation. Since the IgM memory compartment is important for host defense against other encapsulated microbes, we hypothesized that IgM memory B-cells levels may influence resistance and susceptibility to CN. We determined the levels of IgM memory B-cells in peripheral blood lymphocytes (PBLs) from 30 HIV+ with (HIV+CN+) and 30 without (HIV+CN-) a history of CN and 20 HIV-uninfected (HIV-) subjects by flow cytometry. Our results showed that HIV+CN+ subjects had significantly lower levels of IgM memory B-cells than both HIV+CN- and HIV- subjects. Among the HIV+ subjects, the CD4 T cell level and the memory IgM level were each independent predictors of cryptococcal status. To assess whether the reduced level of memory IgM B cells in this cohort was associated with cryptococcal disease status, we determined the levels of IgM memory B-cells in banked pre-disease PBLs from 13 HIV+ subjects who subsequently developed cryptococcal disease (HIV+/CN+) and 13 HIV+ subjects who did not (HIV+/CN-) matched by CD4 T cell levels and 26 HIV- subjects, all of whom were enrolled in the Multicenter AIDS Cohort Study (MACS). The results showed that HIV+/CN+ subjects had significantly lower levels of percent IgM memory B-cells than HIV+/CN- and HIV- subjects. In addition, it was again observed that levels of IgM memory cells were a predictor of cryptococcal status. These findings suggest that the status of the IgM memory B-cell pool is a candidate risk factor for cryptococcal susceptibility. In addition, since reduced levels were observed at a CD4 T cell level that is not associated with cryptococcosis, our findings suggest that the status of the IgM memory compartment might reflect an underlying immune defect that enhances the risk of disease, perhaps irrespective of HIV status.