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Clinical and Vaccine Immunology, May 2009, p. 692-698, Vol. 16, No. 5
1071-412X/09/$08.00+0     doi:10.1128/CVI.00485-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Evidence of a Functional B-Cell Immunodeficiency in Adults Who Experience Serogroup C Meningococcal Disease {triangledown}

Rachel A. Foster,1 Jennifer Carlring,1 Michael W. McKendrick,2 Andrew Lees,3 Ray Borrow,4 Robert C. Read,1* and Andrew W. Heath1

Unit of Infection and Immunity, University of Sheffield School of Medicine and Biomedical Science, Sheffield S10 2RX, United Kingdom,1 Fina Biosolutions LLC, 9610 Medical Center Dr., Suite 200, Rockville, Maryland 20850,2 Department of Infectious Disease and Tropical Medicine, Royal Hallamshire Hospital, Sheffield S10 2TN, United Kingdom,3 Vaccine Evaluation Unit, Health Protection Agency, Manchester Royal Infirmary, Manchester, United Kingdom4

Received 22 December 2008/ Returned for modification 2 March 2009/ Accepted 4 March 2009

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.


* Corresponding author. Mailing address: Unit of Infection and Immunity, University of Sheffield School of Medicine, Beech Hill Rd., Sheffield S10 2RX, United Kingdom. Phone: (44) 114 271 3843. Fax: (44) 114 271 3892. E-mail: r.c.read{at}shef.ac.uk

{triangledown} Published ahead of print on 11 March 2009.


Clinical and Vaccine Immunology, May 2009, p. 692-698, Vol. 16, No. 5
1071-412X/09/$08.00+0     doi:10.1128/CVI.00485-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.