Evidence of a functional B-cell immunodeficiency in adults who experience serogroup C meningococcal disease
Evidence of a functional B-cell immunodeficiency in adults who experience serogroup C meningococcal disease
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.
Adolescent, Adult, B-Lymphocytes, Cell Proliferation, Female, Humans, Immunologic Deficiency Syndromes, Lymphocyte Activation, Male, Meningitis, Meningococcal, T-Lymphocytes, Young Adult, Journal Article, Research Support, Non-U.S. Gov't
692-698
Foster, Rachel A.
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Carlring, Jennifer
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McKendrick, Michael W.
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Lees, Andrew
dba4db52-3b05-4414-a801-e3255d068b67
Borrow, Ray
45e5fda9-8300-486e-89ca-323f3ae9c9a6
Read, Robert C.
b5caca7b-0063-438a-b703-7ecbb6fc2b51
Heath, Andrew W.
303a3623-9848-4b85-add7-880752386f0d
May 2009
Foster, Rachel A.
ae78b2b5-6fee-486e-ac49-b755d2d2314c
Carlring, Jennifer
6d5de399-1da9-45e6-83ac-b7735f806348
McKendrick, Michael W.
91cf7c85-c506-466c-a04f-2d9e2c60a2b7
Lees, Andrew
dba4db52-3b05-4414-a801-e3255d068b67
Borrow, Ray
45e5fda9-8300-486e-89ca-323f3ae9c9a6
Read, Robert C.
b5caca7b-0063-438a-b703-7ecbb6fc2b51
Heath, Andrew W.
303a3623-9848-4b85-add7-880752386f0d
Foster, Rachel A., Carlring, Jennifer, McKendrick, Michael W., Lees, Andrew, Borrow, Ray, Read, Robert C. and Heath, Andrew W.
(2009)
Evidence of a functional B-cell immunodeficiency in adults who experience serogroup C meningococcal disease.
Clinical and Vaccine Immunology, 16 (5), .
(doi:10.1128/CVI.00485-08).
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.
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e-pub ahead of print date: March 2009
Published date: May 2009
Keywords:
Adolescent, Adult, B-Lymphocytes, Cell Proliferation, Female, Humans, Immunologic Deficiency Syndromes, Lymphocyte Activation, Male, Meningitis, Meningococcal, T-Lymphocytes, Young Adult, Journal Article, Research Support, Non-U.S. Gov't
Organisations:
Clinical & Experimental Sciences
Identifiers
Local EPrints ID: 346808
URI: http://eprints.soton.ac.uk/id/eprint/346808
ISSN: 1556-6811
PURE UUID: da1d880c-4dcc-4d32-85dd-21a181fdd62d
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Date deposited: 16 Jan 2013 13:27
Last modified: 15 Mar 2024 03:42
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Contributors
Author:
Rachel A. Foster
Author:
Jennifer Carlring
Author:
Michael W. McKendrick
Author:
Andrew Lees
Author:
Ray Borrow
Author:
Andrew W. Heath
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