The immune balance between memory and regulatory B cells in NMO and the changes of the balance after methylprednisolone or rituximab therapy

J Neuroimmunol. 2015 May 15:282:45-53. doi: 10.1016/j.jneuroim.2015.03.016. Epub 2015 Mar 21.

Abstract

We aim to explore the impacts of high dose methylprednisolone therapy (HDMT) and rituximab on circulating B cells in NMO patients. Twenty-two NMO patients in the acute relapse phase were treated with HDMT and 9 patients in the remission stage were treated with rituximab. The frequencies of circulating CD19(+)CD27(+) memory B cell (Bmem), CD19(+)CD24(high)CD38(high) regulatory B cell (Breg) and the B cell production of interleukin (IL)-10 and interferon (IFN)-γ were monitored by flow cytometry before and after the treatment. The frequencies of circulating Bregs and the B cell IL-10 production were significantly lower in NMO patients before HDMT compared to healthy controls. Two weeks' HDMT further reduced the frequencies of Bregs while increased the frequencies of Bmems, which steered the numerical balance between Bmem and Breg in favor of Bmem. Meanwhile, HDMT significantly inhibited the B cell IFN-γ expression. Rituximab exerted its effect through B cell elimination and subsequent B cell repopulation which was characterized by the predominance of Bregs, restored the numerical balance between Breg and Bmem back to an advantageous "Breg>Bmem" status. Therefore, HDMT and rituximab had basically different impacts on B cells in NMO.

Keywords: Memory B cells; Methylprednisolone; Neuromyelitis optica; Regulatory B cells; Rituximab.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Anti-Inflammatory Agents / therapeutic use*
  • Antibodies, Monoclonal, Murine-Derived / therapeutic use*
  • Antigens, CD / metabolism
  • Aquaporin 4 / metabolism
  • B-Lymphocyte Subsets / drug effects*
  • B-Lymphocyte Subsets / immunology
  • Cytokines / metabolism
  • Female
  • Flow Cytometry
  • Humans
  • Male
  • Methylprednisolone / therapeutic use*
  • Middle Aged
  • Neuromyelitis Optica* / drug therapy
  • Neuromyelitis Optica* / immunology
  • Neuromyelitis Optica* / pathology
  • Rituximab
  • Time Factors
  • Young Adult

Substances

  • AQP4 protein, human
  • Anti-Inflammatory Agents
  • Antibodies, Monoclonal, Murine-Derived
  • Antigens, CD
  • Aquaporin 4
  • Cytokines
  • Rituximab
  • Methylprednisolone