title: Evidence of a functional B-cell immunodeficiency in adults who experience serogroup C meningococcal disease.
abstract: After adolescence, the incidence of meningococcal disease decreases with age as a result of the cumulative immunizing effect of repeated nasopharyngeal colonization. Nevertheless, some adults succumb to meningococcal disease, so we hypothesized that this is due to a subtle functional immunological defect. Peripheral blood lymphocytes derived from survivors of serogroup C meningococcal disease and from age- and sex-matched controls were incubated with a polyclonal B-cell activator containing anti-immunoglobulin D (alpha-delta-dex) employed to mimic antigen-specific stimuli encountered during immune responses to bacterial polysaccharides, with and without T-cell activation (using anti-CD3/anti-CD28). Subsequent proliferation and activation of T and B lymphocytes were measured. In patients, T-cell responses to polyclonal stimuli and the delivery of T-cell help to B cells were unimpaired. Levels of B-cell proliferation in response to alpha-delta-dex stimulation alone were low in all samples but were significantly lower in patients than in controls, and these differences were more pronounced with the addition of T-cell help. The data are consistent with the presence of a subtle immunodeficiency in adults who have exhibited susceptibility to meningococcal disease. This defect is manifested as an impaired B-cell response to T-cell-independent type 2 antigens analogous to bacterial capsular polysaccharide.
authors.affiliation: Unit of Infection and Immunity, University of Sheffield School of Medicine and Biomedical Science, Sheffield, United Kingdom.
authors.forename: Rachel A
authors.initials: RA
authors.lastname: Foster
authors.forename: Jennifer
authors.initials: J
authors.lastname: Carlring
authors.forename: Michael W
authors.initials: MW
authors.lastname: McKendrick
authors.forename: Andrew
authors.initials: A
authors.lastname: Lees
authors.forename: Ray
authors.initials: R
authors.lastname: Borrow
authors.forename: Robert C
authors.initials: RC
authors.lastname: Read
authors.forename: Andrew W
authors.initials: AW
authors.lastname: Heath
mesh_terms: D000293:Adolescent; D000328:Adult; D001402:B-Lymphocytes / Q000276:immunology*; D049109:Cell Proliferation; D005260:Female; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000382:microbiology*; D008213:Lymphocyte Activation; D008297:Male; D008585:Meningitis, Meningococcal / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D055815:Young Adult