Preferential induction of autoantibody secretion in polyclonal activation by peptidoglycan and lipopolysaccharide. I. In vitro studies.

Abstract

Peptidoglycan (PG) and lipopolysaccharide (LPS) are bacterial cell wall components that are B cell mitogens and activators of polyclonal antibodies. Using the hemolytic plaque assay and its modifications with protein A-, IgG-, or DNA-coated erythrocytes, we determined the proportions of cells that secrete antibodies specific to various autologous and heterologous antigens in PG- and LPS-stimulated cultures of mouse splenic lymphocytes. Of all PG- and LPS-activated IgM-secreting cells, 47 to 75% produced antibodies specific to mouse IgG; 2.7 to 21% produced IgM antibodies that reacted with bovine IgG; 4.4 to 17%, with single-stranded (ss) DNA; 0.18 to 5.9% with double-stranded (ds) DNA; 0.16 top 3.3%, with bromelin-treated mouse red cells; 0.006 to 0.02%, with intact mouse red cells; and 0.35 to 1.9%, with sheep red cells. A similar distribution of cells secreting these antibodies was observed in unstimulated cultures. However, the absolute numbers of cells secreting these antibodies were substantially higher in the PG- and LPS-stimulated cultures. Similar results were obtained in BALB/c, CBA/H, and C57BL/6 mice. Since these strains of mice have different H-2 types, there was no association of a single H-2 type with the ability to form hgh numbers of autoantibody-secreting cells in vitro. The production of autoantibodies closely resembled polyclonal activation of all immunoglobulin-secreting cells in terms of the kinetics and dose-response. It did not involve any substantial specific anti-PG or anti-LPS response. Further studies on the specificities of polyclonally induced antibodies confirmed the specificity of anti-mouse IgG and anti-ssDNA antibodies. However, the formation of plaques with bovine IgG- or dsDNA-sensitized red cells was due to the cross-reacting anti-mouse IgG or anti-ssDNA antibodies, respectively. These results do not support the popular hypothesis of an equal polyclonal activation of lymphocytes secreting antibodies of all different specificities. Also, if preferential activation of cells secreting rheumatoid factor and anti-ssDNA antibodies occurs in vivo, it may have important pathologic consequences.