Wednesday, 5 December 2018

More Mice in Nature

Knier B, Hiltensperger M, Sie C, Aly L, Lepennetier G, Engleitner T, Garg G, Muschaweckh A, Mitsdörffer M, Koedel U, Höchst B, Knolle P, Gunzer M, Hemmer B, Rad R, Merkler D, Korn T. Myeloid-derived suppressor cells control B cell accumulation in the central nervous system during autoimmunity. Nat Immunol. 2018. doi: 10.1038/s41590-018-0237-5. [Epub ahead of print]

Polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) have been characterized in the context of malignancies. Here we show that PMN-MDSCs can restrain B cell accumulation during central nervous system (CNS) autoimmunity. Ly6G+ cells were recruited to the CNS during experimental autoimmune encephalomyelitis (EAE), interacted with B cells that produced the cytokines GM-CSF and interleukin-6 (IL-6), and acquired properties of PMN-MDSCs in the CNS in a manner dependent on the signal transducer STAT3. Depletion of Ly6G+ cells or dysfunction of Ly6G+ cells through conditional ablation of STAT3 led to the selective accumulation of GM-CSF-producing B cells in the CNS compartment, which in turn promoted an activated microglial phenotype and lack of recovery from EAE. The frequency of CD138+ B cells (plasma cells) in the cerebrospinal fluid (CSF) of human subjects with multiple sclerosis was negatively correlated with the frequency of PMN-MDSCs in the CSF. Thus PMN-MDSCs might selectively control the accumulation and cytokine secretion of B cells in the inflamed CNS.


As mouse EAE has been found to contain neutrophils and MS has B cells, some people are making the case that MS is a problem of neutrophils although if you look in MS, or non-mouse EAE they are vanishingly rare. Here they report that a cell enters the CNS and becomes a neutrophil with suppressor cell function after interaction with B cells. If they depleted them more B cells accumulated in the CNS and activated microglia So may that is the function of Bcells...to activate microglia.


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