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.
Highlights
Pathogen-specific protective IgG levels following natural infection or vaccination can persist for decades, or in some cases for a lifetime, in the apparent absence of the antigen [1]
In agreement with previous results [20], when the analysis was done in terms of the CD27- memory B cells (mBc), RV-mBc were enriched in the CD27-IgG+ subset in healthy adult volunteers (HV), but not in patients prior-RTX
Concerning serological memory, altogether our results suggest that at least a subset of IgM-rheumatoid factors (RF), IgG-anti-cyclic cytrullinated peptide (CCP), and IgG-antidsDNA auto-Abs are mainly maintained by short-lived PC, which are probably in equilibrium with auto-Ag-specific mBc depleted by RTX
Summary
Pathogen-specific protective IgG levels following natural infection or vaccination can persist for decades, or in some cases for a lifetime, in the apparent absence of the antigen [1]. 2) The lifespan of PC is related to the integrated signals through the B-cell receptor, which largely depend on the antigen repetitive nature, and signals obtained through CD4 T-cell help, and is imprinted at the time of the immune response induction [9]. This theory proposes that PC and mBc represent independently regulated populations [11]
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