Helminth infections associated with multiple sclerosis induce regulatory B cells

Ann Neurol. 2008 Aug;64(2):187-99. doi: 10.1002/ana.21438.


Objective: To assess the importance of B-cell control during parasite infections in multiple sclerosis (MS) patients.

Methods: Peripheral blood CD19+ B cells from 12 helminth-infected MS patients, 12 MS patients without infection, 10 patients infected with Trypanosoma cruzi, 8 subjects infected with Paracoccidioides brasiliensis, and 12 healthy control subjects were purified using magnetic cell sorting. Interleukin (IL)-4, IL-6, IL-10, tumor necrosis factor-alpha, lymphotoxin, transforming growth factor-beta, brain-derived neurotrophic factor, and nerve growth factor secretion were evaluated after stimulation with CDw32 L cells and CD40 antibody using enzyme-linked immunosorbent assays. The production of anti-myelin oligodendrocyte glycoprotein IgG and IgM antibodies was evaluated by enzyme-linked immunosorbent spot assays. Cell phenotype was assessed by flow cytometry.

Results: Helminth infections in MS patients created a B-cell population producing high levels of IL-10, dampening harmful immune responses through a mechanism mediated, at least in part, by the ICOS-B7RP-1 pathway. The IL-10-producing B-cell phenotype detected expressed high levels of CD1d and was similar to the one observed in mature naive B2 cells (namely, CD11b(-), CD5(-), CD27(-), and IgD+). Moreover, B cells isolated from helminth-infected MS patients also produced greater amounts of brain-derived neurotrophic factor and nerve growth factor compared with those of normal subjects, T. cruzi-infected subjects, P. brasiliensis-infected subjects, or uninfected MS patients, raising the possibility that these cells may exert a neuroprotective effect on the central nervous system.

Interpretation: Increased production of B-cell-derived IL-10 and of neurotrophic factors are part of the parasite's regulation of host immunity and can alter the course of MS, potentially explaining environmental-related MS suppression observed in areas with low disease prevalence.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Animals
  • B-Lymphocyte Subsets / immunology*
  • B-Lymphocyte Subsets / metabolism*
  • B-Lymphocyte Subsets / parasitology
  • Cell Differentiation / immunology*
  • Female
  • Follow-Up Studies
  • Helminthiasis / immunology*
  • Helminthiasis / metabolism*
  • Helminthiasis / parasitology
  • Humans
  • Interleukin-10 / biosynthesis
  • Male
  • Multiple Sclerosis / immunology*
  • Multiple Sclerosis / parasitology
  • Nerve Growth Factors / biosynthesis
  • Paracoccidioides / immunology
  • Trypanosoma cruzi / immunology
  • Trypanosoma cruzi / parasitology


  • Nerve Growth Factors
  • Interleukin-10