Natural murine autoantibodies and conventional antibodies exhibit similar degrees of antigenic cross-reactivity.

Abstract

Splenic B cells from normal and autoimmune mice were transferred to MHC-compatible xid recipients. Monoclonal antibodies were secreted by the transferred B cells in splenic fragment cultures. These antibodies were evaluated for reactivity and cross-readtivity against a panel of six autoantdgens and two conventional antigens using an ELISA assay. The autoantibodies and conventional antibodits produced in splenic fragment cultures by normal DBA/2 and autoimmune NZB B cells expressed similar degrees of antigenic cross-reactivity.Previous studies have demonstrated that ELISA assays of splenic fragment culture supernatants detect antibodies with affinities of 5 X 106 M' or greater. We therefore also analyzed the cross-reactivitywof monoclonal antibodies derived from hybridomas. This permitted an assessment of antibodies with lower binding affinities. Cross-reactivity was detected more frequently among these hybridomas. Consistent with our earlier observations, hybridoma antibodies specific for conventional antigens exhibited cross-reactivity with a frequency similar to that of antibodies specific for autoantigens.

Theoretical and Experimental Approaches to Generalized Autoimmunity

“…Using the splenic fragment assay to compare the number of cells secreting antibodies reactive with a panel of conventional and autoantigens, we found that antibodies produced by cells from autoimmune strains were no more crossreactive than those from normal straitis (Klinmati et al 1988a). Moreover, those B cells producing crossreactive antibodies were no more reactive with autoantigens than with conventional antigens (Klinman et al 1988a).…”

“…Similarly, established tolerance also can be broken by such stimulants. Moreover, polyclonal immune stimulation is an important feature of the autoantibody production in murine lupus (Moutsopoulos et al 1977, Manny et al 1979, Klinman & Steinberg 1987, Klinman et al 1988a. 1988c.…”

Two-dimensional electrophresis and mass spectrometry identification of proteins bound by a murine monoclonal anti-cardiolipin antibody: A powerful technique to characterize the cross-reactivity of a single autoantibody

“…This property of antigenic cross-reactivity has been observed with both conventional antibodies, i.e., those produced after immunization [2], and autoantibodies synthesized by individuals with autoimmune disorders [3]. Such cross-reactivity seems to be particularly frequent among autoantibodies produced during systemic lupus erythematosus (SLE), an autoimmune disease developed by humans [4] and certain strains of mice [5], and characterized by the presence of autoantibodies directed against various components of the cell, namely nucleic acids, histones, ribonucleoproteins (RNP), cytoplasmic proteins, and anionic phospholipids.…”

Induction of myosin cross-reactive antibody and cytolytic T cell responses in mice with Streptococcus pyogenes

“…Furthermore, sufficient evidence has been presented to show that streptococcal infections are capable of inducing crossreactive antibody responses in both humans and laboratory animals (Zabriskie and Freimer 1966;van de Rijn et al 1977;Cunningham et al 1988). However, it is difficult to assign a primary role for the cross-reactive antibodies since evidence that can ascribe pathogenic potential to such antibodies is lacking (Neu et al 1993) and because normal healthy individuals exhibit low levels of self-reactive natural antibodies in their sera without any resultant complications (Klinman et al 1988).…”