title: Reduction of CD1d expression in vivo minimally affects NKT-enhanced antibody production but boosts B-cell memory.
abstract: The CD1d-binding glycolipid α-galactosylceramide exerts potent adjuvant effects on T-dependent humoral immunity. The mechanism is driven by cognate interaction between CD1d-expressing B cells and TCR-expressing type I CD1d-restricted NKT cells. Thus, far positive effects of alpha-galactosylceramide have been observed on initial and sustained antibody titers as well as B-cell memory. Following vaccination, each of these features is desirable, but good B-cell memory is of paramount importance for long-lived immunity. We therefore tested the hypothesis that CD1d expression in vivo differentially affects initial antibody titers versus B-cell memory responses. CD1d(+/+) and CD1d(+/-) mice were generated and immunized with antigen plus CD1d ligand before analysis of cytokine expression, CD40L expression, initial and longer term antibody responses and B-cell memory. As compared with CD1d(+/+) controls, CD1d(+/-) mice had equivalent numbers of total NKT cells, lower cytokine production, fewer CD40L-expressing NKT cells, lower initial antibody responses, similar long-term antibody responses and higher B-cell memory. Our data indicate that weak CD1d antigen presentation may facilitate good B-cell memory without compromising antibody responses. This work may impact vaccine design since over-stimulation of NKT cells at the time of vaccination may not lead to optimal B-cell memory.
authors.affiliation: Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
authors.forename: Gillian A
authors.initials: GA
authors.lastname: Lang
authors.forename: Amy M
authors.initials: AM
authors.lastname: Johnson
authors.forename: T Scott
authors.initials: TS
authors.lastname: Devera
authors.forename: Sunil K
authors.initials: SK
authors.lastname: Joshi
authors.forename: Mark L
authors.initials: ML
authors.lastname: Lang
mesh_terms: D000818:Animals; D000917:Antibody Formation / Q000235:genetics; D055610:Antigens, CD1d / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D023201:CD40 Ligand / Q000235:genetics / Q000378:metabolism; D002450:Cell Communication; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D005260:Female; D005699:Galactosylceramides / Q000276:immunology / Q000378:metabolism; D007156:Immunologic Memory / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D055611:Natural Killer T-Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism*
chemical_list: D055610:Antigens, CD1d; D016207:Cytokines; D005699:Galactosylceramides; C493154:alpha-galactosylceramide; D023201:CD40 Ligand