Interleukins and IgA synthesis. Human and murine interleukin 6 induce high rate IgA secretion in IgA-committed B cells.

TLDR

The study aimed to investigate whether cytokines could induce Ig synthesis in murine PP B cells. Freshly isolated murine PP B cells were cultured with ten cytokines, including IL‑1α, IL‑2, IL‑4, IL‑5, IL‑6, IL‑7, IFN‑γ, TNF‑α, and TGF‑β. IL‑5 and both mouse and human IL‑6 increased IgA secretion, with IL‑6 producing a stronger (~7‑fold) effect that was not accompanied by IgM/IgG production or B‑cell proliferation, was blocked by anti‑IL‑6 antiserum, and indicates IL‑6 drives terminal differentiation of PP B cells into IgA‑secreting plasma cells.

Abstract

Freshly isolated murine PP B cells were cultured with 10 different cytokines, including IL-1 alpha, IL-2, IL-4, IL-5, IL-6, IL-7, IFN-gamma, TNF-alpha, and TGF-beta, to investigate a possible role for these cytokines in induction of Ig synthesis. Of interest was the finding that only IL-5 and both mouse recombinant (mr) and human recombinant (hr) IL-6 enhanced IgA synthesis. The effect was greater with either mrIL-6 or hrIL-6 than with mrIL-5. IL-6 induced cycling mIgA+ PP B cells to secrete high levels of IgA (approximately 7-fold increase over control). Of importance was the finding that mrIL-6 had little effect on secretion of IgM or IgG by PP B cell cultures. hrIL-6 also increased IgA secretion by PP B cells and this enhancement was abolished by a goat anti-hrIL-6 antiserum. mrIL-6 did not cause B cell proliferation but induced a sharp increase in numbers of B cells secreting IgA. Isotype-switching was not a mechanism for this marked increase in IgA synthesis since mIgA- PP B cells were not induced to secrete IgA by mrIL-6. From these studies we conclude that IL-6 plays an important role in promoting the terminal differentiation of PP B cells to IgA-secreting plasma cells.