title: IgM(+) memory B cell expression predicts HIV-associated cryptococcosis status.
abstract: 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.
authors.affiliation: Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY, USA.
authors.forename: Krishanthi
authors.initials: K
authors.lastname: Subramaniam
authors.forename: Brian
authors.initials: B
authors.lastname: Metzger
authors.forename: Lawrence H
authors.initials: LH
authors.lastname: Hanau
authors.forename: Alice
authors.initials: A
authors.lastname: Guh
authors.forename: Lisa
authors.initials: L
authors.lastname: Rucker
authors.forename: Sheila
authors.initials: S
authors.lastname: Badri
authors.forename: Liise-Anne
authors.initials: LA
authors.lastname: Pirofski
mesh_terms: D000328:Adult; D001402:B-Lymphocytes / Q000276:immunology*; D015331:Cohort Studies; D003453:Cryptococcosis / Q000150:complications* / Q000276:immunology; D005260:Female; D005786:Gene Expression Regulation; D015658:HIV Infections / Q000150:complications*; D006801:Humans; D007075:Immunoglobulin M / Q000235:genetics / Q000378:metabolism*; D007156:Immunologic Memory; D008297:Male; D008875:Middle Aged
chemical_list: D007075:Immunoglobulin M