Synthesis of abnormal immunoglobulins by hybridomas from autoimmune "viable motheaten" mutant mice.

Abstract

Abstract. Secretory defects in abnormal plasma cells, called Mott cells, that appear in lymphoid tissues of spontaneously autoimmune, "viable motheaten" (me°/me°) mice lead to deposition of immunoglobulin in RER-bound vesicles. Such vesicles have been termed Russell bodies. Cells with Russell bodies can also be observed rarely in normal animals, usually as a result of extreme antigenic loads or pathologic states . To understand why these abnormal cells appear commonly in mev/me°mice, we have established a panel of hybridomas that contain Russell bodies . Using immunochemical analysis and immunoelectron microscopy, we have characterized the secretory defects. Although these hybridoma cells synthesize a normal size heavy chain and it associates with light chain, the Russell bodies have many characteristics of inclusion bodies, which commonly appear in cells synthesizing mutant proteins and often are associated with incompletely or abnormally folded proteins . Pulse-chase experiments showed that immunoglobulins M UTATIONS that disrupt biological processes provide insight into the ordering of these processes. Many mutations that affect the immune system cause multiple pleiotropic abnormalities, emphasizing the complexity and interrelatedness of the immune, endocrine, and nervous systems (33) . One of the most deleterious mutations identified is "viable motheaten" (me,),' a spontaneous, single gene mutation that occurred on the C57BL/6J background (34) . me, mice have a mean life span of 9 wk. Autoimmune pulmonary lesions are the proximal cause of death. Homozygotes (me°/me,) develop glomerulonephritis, have multiple autoantibodies, and serum IgM levels are increased 25-to 50-fold above levels found in littermate controls (35) . Abnormal plasma cells, called Mott cells, are found initially at -4 wk of age . These cells have discrete gly-1 . Abbreviations used in this paper: BiP, binding protein ; Endo H, endoglycosidase H; me', viable motheaten; PAS, periodic acid-Schiffs ; SACI, Staphylococcus aureus, Cowan strain I ; TEM, transmission electron microscopy.

ER storage diseases: a role for ERGIC-53 in controlling the formation and shape of Russell bodies

“…RB are induced also by other Ig isotypes, when the CH1 domain is missing (Kaloff and Haas, 1995). Their presence correlates with the accumulation of detergentinsoluble Ig, which can neither be transported to the Golgi nor be dispatched to the cytosol for degradation (Schweitzer et al, 1991;Valetti et al, 1991).…”

A different sort of Mott cell.

“…These cells are lymphocytes that produce large amounts of immunoglobulin contained mainly in large vesicles, the so-called Russell bodies (2,3). When viewed under the light microscope, Mott (4)(5)(6)(7).…”

“…Some 5 X 106 cells were washed in protein-free RPMI 1640 medium, suspended in 500 ml of the same medium, and mixed with [5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] pAg of circular or linearized DNA. The mixture was electroporated with a Cell Porator (BRL) at 330 IkF, 285 V, low resistance.…”

Uptake of maternal immunoglobulins in the enterocytes of suckling piglets: improved detection with a streptavidin-biotin bridge gold technique.

“…When we tried to localize endogenous porcine immunoglobulins in the present study with colloidal gold probes, the first two conditions were not the major limiting factors. Intracellular antigens, including endogenous immunoglobulins, can be detected with epoxy (18, [34][35][36]41) and Lowicryl (8) resins. Furthermore, we were able to detect the accumulation of immunoglobulins of maternal origin in small intestinal enterocytes ofsuckling piglets 1-4 days of age even in Spurr's resin-embedded, osmicated tissues (23).…”