Uptake and presentation of myelin basic protein by normal human B cells

PLoS One. 2014 Nov 17;9(11):e113388. doi: 10.1371/journal.pone.0113388. eCollection 2014.

Abstract

B cells may play both pathogenic and protective roles in T-cell mediated autoimmune diseases such as multiple sclerosis (MS). These functions relate to the ability of B cells to bind and present antigens. Under serum-free conditions we observed that 3-4% of circulating B cells from healthy donors were capable of binding the MS-associated self-antigen myelin basic protein (MBP) and of presenting the immunodominant peptide MBP85-99, as determined by staining with the mAb MK16 recognising the peptide presented by HLA-DR15-positive cells. In the presence of serum, however, the majority of B cells bound MBP in a complement-dependent manner, and almost half of the B cells became engaged in presentation of MBP85-99. Even though complement receptor 1 (CR1, CD35) and CR2 (CD21) both contributed to binding of MBP to B cells, only CR2 was important for the subsequent presentation of MBP85-99. A high proportion of MBP85-99 presenting B cells expressed CD27, and showed increased expression of CD86 compared to non-presenting B cells. MBP-pulsed B cells induced a low frequency of IL-10-producing CD4+ T cells in 3 out of 6 donors, indicating an immunoregulatory role of B cells presenting MBP-derived peptides. The mechanisms described here refute the general assumption that B-cell presentation of self-antigens requires uptake via specific B-cell receptors, and may be important for maintenance of tolerance as well as for driving T-cell responses in autoimmune diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • B-Lymphocytes / immunology*
  • B-Lymphocytes / metabolism
  • Cell Proliferation
  • Cells, Cultured
  • Humans
  • Immunodominant Epitopes / immunology*
  • Immunodominant Epitopes / metabolism
  • Interleukin-10 / immunology*
  • Interleukin-10 / metabolism
  • Multiple Sclerosis / immunology*
  • Multiple Sclerosis / metabolism
  • Myelin Basic Protein / immunology*
  • Myelin Basic Protein / metabolism
  • Peptide Fragments / immunology*
  • Peptide Fragments / metabolism
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism

Substances

  • Immunodominant Epitopes
  • Myelin Basic Protein
  • Peptide Fragments
  • myelin basic protein 85-99
  • Interleukin-10

Grant support

MKB received funding from The Danish Multiple Sclerosis Society, grant number 959531218. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.