Saturday, 12 November 2016

B regs make T regs.

Pennati A, Ng S, Wu Y, Murphy JR, Deng J, Rangaraju S, Asress S, Blanchfield JL, Evavold B, Galipeau J. Regulatory B cells induce formation of IL-10 expressing T cells in mice with autoimmune neuroinflammation. J Neurosci. 2016 Nov 7. pii: 1994-16. [Epub ahead of print]

Although B cells are traditionally known for their role in propagating pro-inflammatory immune responses, their immunosuppressive effects have only begun to be recently appreciated. How these regulatory B cells (Bregs) suppress the immune response remains to be worked out in detail. In this paper we show that Bregs can induce formation of conventional FoxP3+ regulatory T cells (Tregs), as well as a more recently described CD49b+CD223+ regulatory T cell subset, known as type 1 regulatory T cells (Tr1). When Bregs are transferred into mice with experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis, they home to the spleen and mesenteric lymph nodes, leading to an expansion of Tregs and Tr1 in vivo Tregs and Tr1 cells are also found in greater proportions in the central nervous system of mice with EAE treated with Bregs and are correlated with remission of symptoms. The discovery that Bregs induce the formation of regulatory T cell subsets in vivo may herald their use as immunosuppressive agents in adoptive cellular therapies for autoimmune pathologies.

SIGNIFICANCE STATEMENT:

Although B cells are traditionally known for their role in propagating pro-inflammatory immune responses, their immunosuppressive effects have only begun to be recently appreciated. How regulatory B cells (Bregs) suppress the immune response remains to be fully understood. In this paper we show that Bregs can induce formation of conventional regulatory T cells (Tregs) as well as type 1 regulatory T cells (Tr1). When Bregs are transferred into mice with experimental autoimmune encephalomyelitis (EAE), they home to secondary lymphoid organs, leading to an expansion of Tregsand Tr1 in vivo Tregs and Tr1 cells are also found in greater proportions in the central nervous system of mice with EAE treated with Bregs and are correlated with remission of symptoms.

When I was a scienctific ameoba, B suppressor cells were the rage so abit surprising that only recently ( thirty years on) they are being recognised, as being new. So in this study we have B regs making Tregs and Tr1's which make IL-10 and herald the way forward. So it means that when you wipe out B cells then you are affecting a balance of removing pathogenic cells and regulatory cells. However is they way forward?
I'm not so sure. Dogma in immunology was make Th1 cells become Th2 cells which produce things like IL-4, and IL-10 and IL-13. This is fine in T cell mediated EAE, but we know in established EAE and MS that antibody-producing B cells are a problem and so if you make IL-10 this be just the problem you don't want. I think you don't want Th1, Th2 or Th17. Maybe unsurprsingly treatment with IL-10 has already bombed in MS.
Likewise whilst Tregs are now the mechanism of choice to both immune responses, we still haven't explained why daclizumab HYP works when it causes a substantial depletion of Tregs...actually I may have the answer but I'll explain later:-). When trying to seek treatments we have to think we are trying to treat a human condition and not just an immune mechanism...when we do that maybe we will have more successful trials.

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