title: Distinct Differentiation Programs Triggered by IL-6 and LPS in Teleost IgM(+) B Cells in The Absence of Germinal Centers.
abstract: Although originally identified as a B cell differentiation factor, it is now known that mammalian interleukin-6 (IL-6) only regulates B cells committed to plasma cells in response to T-dependent (TD) antigens within germinal centers (GCs). Even though adaptive immunity is present in teleost fish, these species lack lymph nodes and GCs. Thus, the aim of the present study was to establish the role of trout IL-6 on B cells, comparing its effects to those induced by bacterial lipopolysaccharide (LPS). We demonstrate that the effects of teleost IL-6 on naïve spleen B cells include proliferation, activation of NF-κB, increased IgM secretion, up-regulation of Blimp1 transcription and decreased MHC-II surface expression that point to trout IL-6 as a differentiation factor for IgM antibody-secreting cells (ASCs). However, LPS induced the secretion of IgM without up-regulating Blimp1, driving the cells towards an intermediate activation state in which antigen presenting mechanisms are elicited together with antibody secretion and expression of pro-inflammatory genes. Our results reveal that, in trout, IL-6 is a differentiation factor for B cells, stimulating IgM responses in the absence of follicular structures, and suggest that it was after follicular structures appeared that this cytokine evolved to modulate TD responses within the GC.
authors.affiliation: Centro de Investigación en Sanidad Animal (CISA-INIA), Madrid, Spain.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Abós
authors.affiliation: Scottish Fish Immunology Research Centre, University of Aberdeen, Aberdeen, UK.
authors.forename: Tiehui
authors.initials: T
authors.lastname: Wang
authors.affiliation: Centro de Investigación en Sanidad Animal (CISA-INIA), Madrid, Spain.
authors.forename: Rosario
authors.initials: R
authors.lastname: Castro
authors.affiliation: Centro de Investigación en Sanidad Animal (CISA-INIA), Madrid, Spain.
authors.forename: Aitor G
authors.initials: AG
authors.lastname: Granja
authors.affiliation: Centro de Investigación en Sanidad Animal (CISA-INIA), Madrid, Spain.
authors.forename: Esther
authors.initials: E
authors.lastname: Leal
authors.affiliation: Department of Biological Sciences, University of Alberta, Alberta, Canada.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Havixbeck
authors.affiliation: Centro de Investigación en Sanidad Animal (CISA-INIA), Madrid, Spain.
authors.forename: Alfonso
authors.initials: A
authors.lastname: Luque
authors.affiliation: Department of Biological Sciences, University of Alberta, Alberta, Canada.
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Barreda
authors.affiliation: Scottish Fish Immunology Research Centre, University of Aberdeen, Aberdeen, UK.
authors.forename: Chris J
authors.initials: CJ
authors.lastname: Secombes
authors.affiliation: Centro de Investigación en Sanidad Animal (CISA-INIA), Madrid, Spain.
authors.forename: Carolina
authors.initials: C
authors.lastname: Tafalla
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D049109:Cell Proliferation / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D018858:Germinal Center / Q000276:immunology*; D007075:Immunoglobulin M / Q000096:biosynthesis* / Q000276:immunology; D015850:Interleukin-6 / Q000276:immunology / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000276:immunology / Q000494:pharmacology*; D016328:NF-kappa B / Q000276:immunology; D017686:Oncorhynchus mykiss / Q000276:immunology*; D000074462:Positive Regulatory Domain I-Binding Factor 1 / Q000096:biosynthesis; D014158:Transcription, Genetic / Q000187:drug effects; D015533:Transcriptional Activation / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D007075:Immunoglobulin M; D015850:Interleukin-6; D008070:Lipopolysaccharides; D016328:NF-kappa B; D000074462:Positive Regulatory Domain I-Binding Factor 1