title: Type I cytokine profiles of human naïve and memory B lymphocytes: a potential for memory cells to impact polarization.
abstract: B cells bifurcating along 'type 1' or 'type 2' pathways under the influence of polarizing cytokines can, in turn, influence the direction of an immune response. Here, we compare the capacity of human B cells residing within naïve and memory compartments to participate in type 1 polarizing responses. B-cell receptor (BCR) engagement provided the main signal for interleukin (IL)-12Rbeta1 expression in the two subsets: this was potentiated by CD154 together with interferon-gamma (IFN-gamma) but inhibited by IL-12. IL-12Rbeta2 could be induced on a minority of B cells by the same signals, and also by IFN-gamma alone. WSX-1, a receptor for IL-27, was expressed in both subsets with no evidence for its regulation by the signals studied. While neither subset was capable of secreting much IL-12 p70, memory B cells could produce a small amount of IL-12 p40 on CD40 ligation. Memory B cells also, exclusively, expressed IL-23 p19 mRNA on BCR triggering. Importantly, products of appropriately stimulated memory--but not naive--B cells were shown to promote the synthesis of IFN-gamma in uncommitted T-helper cells. The data indicate an equal capacity for naïve and memory B cells to respond within a type 1 polarizing environment. Although poorly equipped for initiating type 1 responses, B cells--by virtue of the memory subset--reveal a capacity for their maintenance and amplification following T-dependent signalling.
authors.affiliation: Institute of Immunology, Zagreb, Croatia. agagro@imz.hr
authors.forename: Alenka
authors.initials: A
authors.lastname: Gagro
authors.forename: Drazen
authors.initials: D
authors.lastname: Servis
authors.forename: Alma-Martina
authors.initials: AM
authors.lastname: Cepika
authors.forename: Kai-Michael
authors.initials: KM
authors.lastname: Toellner
authors.forename: Gillian
authors.initials: G
authors.lastname: Grafton
authors.forename: Dale R
authors.initials: DR
authors.lastname: Taylor
authors.forename: Srecko
authors.initials: S
authors.lastname: Branica
authors.forename: John
authors.initials: J
authors.lastname: Gordon
mesh_terms: D016175:B-Lymphocyte Subsets / Q000276:immunology*; D019013:CD40 Antigens / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis*; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D006801:Humans; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12 / Q000096:biosynthesis; D020381:Interleukin-17 / Q000378:metabolism; D053759:Interleukin-23; D053760:Interleukin-23 Subunit p19; D007378:Interleukins / Q000096:biosynthesis; D008211:Lymphocyte Cooperation / Q000276:immunology; D011947:Receptors, Antigen, B-Cell / Q000276:immunology; D018123:Receptors, Interleukin / Q000378:metabolism; D053707:Receptors, Interleukin-12; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D015398:Signal Transduction / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology
chemical_list: D019013:CD40 Antigens; D016207:Cytokines; C464462:IL17D protein, human; C508840:IL23A protein, human; D020381:Interleukin-17; D053759:Interleukin-23; D053760:Interleukin-23 Subunit p19; D007378:Interleukins; D011947:Receptors, Antigen, B-Cell; D018123:Receptors, Interleukin; D053707:Receptors, Interleukin-12; D018664:Interleukin-12; D007371:Interferon-gamma