title: Impaired maintenance of naturally acquired T-cell memory to the meningococcus in patients with B-cell immunodeficiency.
abstract: 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.
authors.affiliation: Cellular and Molecular Medicine, School of Medical Sciences, University of Bristol, Bristol, United Kingdom.
authors.forename: Begonia
authors.initials: B
authors.lastname: Morales-Aza
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Glennie
authors.forename: Tomaz Pereira
authors.initials: TP
authors.lastname: Garcez
authors.forename: Victoria
authors.initials: V
authors.lastname: Davenport
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Johnston
authors.forename: Neil A
authors.initials: NA
authors.lastname: Williams
authors.forename: Robert S
authors.initials: RS
authors.lastname: Heyderman
mesh_terms: D000328:Adult; D000361:Agammaglobulinemia / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D000942:Antigens, Bacterial / Q000276:immunology / Q000378:metabolism; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D019013:CD40 Antigens / Q000276:immunology / Q000378:metabolism; D023201:CD40 Ligand / Q000276:immunology / Q000378:metabolism; D016022:Case-Control Studies; D005260:Female; D005434:Flow Cytometry; D040181:Genetic Diseases, X-Linked / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D006801:Humans; D053307:Hyper-IgM Immunodeficiency Syndrome, Type 1 / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D007156:Immunologic Memory / Q000276:immunology*; D008213:Lymphocyte Activation; D008297:Male; D008589:Meningococcal Infections / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008875:Middle Aged; D009345:Neisseria meningitidis / Q000472:pathogenicity*; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D055815:Young Adult
chemical_list: D000942:Antigens, Bacterial; D019013:CD40 Antigens; D023201:CD40 Ligand