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Blood, 30 April 2009, Vol. 113, No. 18, pp. 4206-4212.
Prepublished online as a Blood First Edition Paper on February 6, 2009; DOI 10.1182/blood-2008-08-171587.


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IMMUNOBIOLOGY

Impaired maintenance of naturally acquired T-cell memory to the meningococcus in patients with B-cell immunodeficiency

Begonia Morales-Aza1,*, Sarah J. Glennie1,2,*, Tomaz Pereira Garcez3, Victoria Davenport4, Sarah L. Johnston3, Neil A. Williams1, and Robert S. Heyderman1,2

1 Cellular and Molecular Medicine, School of Medical Sciences, University of Bristol, Bristol, United Kingdom; 2 Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Blantyre, Malawi; 3 Department of Immunology, North Bristol National Health Service (NHS) Trust, Bristol, United Kingdom; and 4 Faculty of Applied Sciences, University of West of England, Frenchay Campus, Bristol, United Kingdom

The importance of T cells in the generation of antigen-specific B-cell immunity has been extensively described, but the role B cells play in shaping T-cell memory is uncertain. In healthy controls, exposure to Neisseria meningitidis in the upper respiratory tract is associated with the generation of memory T cells in the mucosal and systemic compartments. However, we demonstrate that in B cell–deficient subjects with X-linked agammaglobulinemia (XLA), naturally acquired T-cell memory responses to meningococcal antigens are reduced compared with healthy control patients. This difference is not found in T-cell memory to an obligate respiratory pathogen, influenza virus. Accordingly, we show that meningococcal antigens up-regulate major histocompatibility complex (MHC) class II, CD40, CD86/80 expression on mucosal and systemic associated B cells and that antigen presentation stimulates T-cell proliferation. A similar reduction in N meningitidis but not influenza antigen–specific T-cell memory was observed in subjects with X-linked hyper IgM syndrome (X-HIM), implicating the interaction of CD40-CD40L in this process. Together, these data implicate B cells in the induction and maintenance of T-cell memory to mucosal colonizing bacteria such as N meningitidis and highlight the importance of B cells beyond antibody production but as a target for immune reconstitution.


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