Distinct Differentiation Programs Triggered by IL-6 And LPS in Teleost IgM+ B Cells in the Absence of Germinal Centers

Beatriz Abós, Tiehui Wang, Rosario Castro, Aitor G. Granja, Esther Leal, Jeffrey Havixbeck, Alfonso Luque, Daniel R. Barreda, Chris J. Secombes, Carolina Tafalla

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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.
Original languageEnglish
Article number30004
Pages (from-to)1-16
Number of pages16
JournalScientific Reports
Early online date2 Aug 2016
Publication statusPublished - 2016

Bibliographical note

We would like to thank Lucia Gonzalez and Maria Sanz for technical assistance. Professor Øystein Evensen is also acknowledged for providing us with the inactivated IPNV. This work was supported by the European Research Council (ERC Starting Grant 2011 280469) and by the European Commission under the 7th Framework Programme for Research and Technological Development (FP7) of the European Union (Grant Agreement 311993 TARGETFISH). T. W. received funding from the MASTS pooling initiative (The Marine Alliance for Science and Technology for Scotland). MASTS is funded by the Scottish Funding Council (grant reference HR09011).


  • B cells
  • Interleukin 6 (IL-6)
  • lipopolysaccharide (LPS);
  • trout
  • anti-body-secreting cells (ASCs)


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