Simultaneous assessment of rotavirus-specific memory B cells and serological memory after B cell depletion therapy with rituximab

PLoS One. 2014 May 12;9(5):e97087. doi: 10.1371/journal.pone.0097087. eCollection 2014.

Abstract

The mechanisms that contribute to the maintenance of serological memory are still unclear. Rotavirus (RV) memory B cells (mBc) are enriched in IgM(+) and CD27- subpopulations, which are associated with autoimmune diseases pathogenesis. In patients with autoimmune diseases treated with Rituximab (RTX), some autoantibodies (auto-Abs) decrease after treatment, but other auto-Abs and pathogen-specific IgG Abs remain unchanged. Thus, maintenance of autoimmune and pathogen-specific serological memory may depend on the type of antigen and/or Ab isotype evaluated. Antigen-specific mBc and antigen-specific Abs of different isotypes have not been simultaneously assessed in patients after RTX treatment. To study the relationship between mBc subpopulations and serological memory we characterized total, RV- and tetanus toxoid (TT)-specific mBc by flow cytometry in patients with autoimmune diseases before and after treatment with RTX. We also measured total, RV- and TT-Abs, and some auto-Abs by kinetic nephelometry, ELISA, and EliA tests, respectively. Minor differences were observed between the relative frequencies of RV-mBc in healthy controls and patients with autoimmune disease. After RTX treatment, naïve Bc and total, RV- and TT-specific mBc [IgM(+), switched (IgA(+)/IgG(+)), IgM(+) only, IgD(+) only, and CD27- (IgA(+)/IgG(+)/IgM(+))] were significantly diminished. An important decrease in total plasma IgM and minor decreases in total IgG and IgA levels were also observed. IgM rheumatoid factor, IgG anti-CCP, and IgG anti-dsDNA were significantly diminished. In contrast, RV-IgA, RV-IgG and RV-IgG1, and TT-IgG titers remained stable. In conclusion, in patients with autoimmunity, serological memory against RV and TT seem to be maintained by long-lived plasma cells, unaffected by RTX, and an important proportion of total IgM and serological memory against some auto-antigens seem to be maintained by short-lived plasma cells, dependent on mBc precursors depleted by RTX.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antibodies, Monoclonal, Murine-Derived / pharmacology*
  • Autoantigens / immunology
  • B-Lymphocyte Subsets / drug effects
  • B-Lymphocyte Subsets / immunology
  • B-Lymphocytes / drug effects*
  • B-Lymphocytes / immunology*
  • Female
  • Humans
  • Immunoglobulin M / blood
  • Immunologic Memory / drug effects*
  • Lymphocyte Depletion / methods*
  • Male
  • Middle Aged
  • Rituximab
  • Rotavirus / immunology*
  • Species Specificity

Substances

  • Antibodies, Monoclonal, Murine-Derived
  • Autoantigens
  • Immunoglobulin M
  • Rituximab

Grants and funding

This work was supported by Pontificia Universidad Javeriana (ID3867). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.