Submitted August 1, 2008
Accepted January 22, 2009
Impaired maintenance of naturally acquired T cell memory to the meningococcus in individuals with B cell immunodeficiency
Begonia Morales-Aza, Sarah J Glennie*, Tomaz Pereira Garcez, Victoria Davenport, Sarah L Johnston, Neil A Williams, and Robert S Heyderman
Cellular and Molecular Medicine, School of Medical Sciences, University of Bristol, Bristol, United Kingdom
Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Blantyre, Malawi
Department of Immunology, North Bristol NHS Trust, Bristol, United Kingdom
Faculty of Applied Sciences, University of West of England, Bristol, United Kingdom
* Corresponding author; email: sarah.glennie{at}liverpool.ac.uk.
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 individuals, 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 controls. This difference is not seen in T cell memory to an obligate respiratory pathogen, influenza virus. Accordingly, we show that meningococcal antigens upregulate 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 seen 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.
