Development of plasmacytoid cells with Russell bodies in autoimmune "viable motheaten" mice

Abstract

Mice homozygous for the autosomal recessive mutation "viable motheaten" (mev) are severely immunodeficient, show polyclonal B-cell activation, and express multiple autoantibodies over a maximum life span of 25 weeks. Lymphoid tissues from these mice contain large numbers of atypical plasma cells in which discrete glycoprotein inclusions are found within the endoplasmic reticulum. Such plasma cells are termed "Mott cells," and the inclusions are called "Russell bodies." Dense accumulations of Mott cells are present in the marginal zones of the spleen and in the lymph nodes of mev/mev mice. Russell bodies in Mott cells from mev/mev mice contain immunoglobulin (Ig) as shown by immunofluorescence microscopy at the light-microscopic level and by indirect protein A-immunogold localization at the electron-microscopic level. Ultrastructural analyses reveal the presence of amorphous, lamellar, and crystalline Russell bodies. These Ig crystals have a periodicity of 150-190 A. Lymph node cell preparations which were enriched in Mott cells by velocity sedimentation failed to secrete Ig in a polyclonal reverse plaque assay. An obligate role of the thymus in Mott cell development is evidenced by the absence of Mott cells in neonatally thymectomized mev/mev mice and in mice doubly homozygous for the nude (nu) and mev mutations. These data suggest that Mott cells in mev/mev mice are thymic-dependent plasmacytoid cells resulting from chronic B-cell activation accompanied by impaired Ig secretion.