Self‐Tolerance Maintained by Active Suppressor Mechanisms

1986

Cultured peritoneal cells from untreated mice, after 3 days of in vitro culture, produce autoantibodies against bromelain-treated isologous erythrocytes. The autoantibody response varies with both age and gender. The effects of age and gender were demonstrated by culturing peritoneal cells using limiting dilution techniques. In neonatal mice there were no precursor cells that differentiated into autoantibody secretors. Cells from female mice gave higher responses than cells from males, and the effect was more pronounced in cells from older mice and cultures to which lipopolysaccharide/dextran sulfate (LPS/DS) had been added. Various cell separation and cell mixing experiments indicated that a non-B-cell, nonadherent cell was involved in the higher autoimmunity detected in the presence of LPS/DS in female and older mice. It is thus possible that low autoimmune responses are due to the absence or unresponsiveness of accessory cells rather than potentially autoimmune B-cells.

Section: Discussionmentioning

confidence: 99%

Limiting Dilution Analysis of Age- and Gender-Related Differences in Autoantibody Production against Bromelain-Modified RBC

Errington

1986

“…They contain, however, relatively large numbers of plaque-forming cells (PFC) against bromelain-treated syngeneic or allogeneic erythrocytes (Br.MRBC) [4][5][6], and the numbers of anti-Br.MRBC PFC remarkably increase by the injection of bacterial lipopolysaccharide (LPS) [7,8], The numbers of anti-Br.MRBC PFC were shown to increase with the age of mice in both untreated or LPS-injected individuals [9,10], As a reason for the increase in PFC numbers, it was suggested that activities of suppressor cells decreased with age so that B cell clones became liable to expand or to differentiate into antibody-forming cells spontaneously or in response to LPS [7,10,11]. In the preceding paper [8] ontogénie development of anti-Br.MRBC PFC re sponse was examined, and it was shown that splenic anti-Br.MRBC PFC response devel oped gradually during the first 4 weeks of age.…”

Section: -mentioning

confidence: 99%

Lipopolysaccharide-Induced Autoantibody Response

Fujiwara¹,

Kariyone²

1981

In spleen of normal mice, there are relatively large numbers of plaque-forming cells (PFC) against syngeneic or allogeneic red blood cells treated with bromelain (Br. MRBC) and the numbers of PFC remarkably increase by the injection of bacterial lipopolysacchaiide (LPS). In this report, age-related change in the anti-Br. MRBC PFC response was studied in vivo and in vitro. It was revealed that mean numbers of splenic anti-Br. MRBC PFC increased in both untreated and LPS-injected mice with age (3–14 months). The increase in anti-Br.MRBC PFC detected in LPS-stimulated spleen was dependent on the numbers of PFC in untreated spleen, but not related to the numbers of anti-TNP PFC nor the degree of ³H-thymidine incorporation assessed in in vitro culture. These results imply that enhanced anti-Br.MRBC PFC response was not merely due to polyclonal activation of B lymphocytes. Reasons for increased PFC numbers were analyzed in special references to suppressor activities. The experimental results were obtained suggesting that suppressors were not involved in anti-Br.MRBC PFC response. There were also no marked differences in the acceptability of suppressive signals between young and older spleen cells. It was concluded that hightened anti-Br.MRBC PFC response in older mice might be due to spontaneous increase in the size of Br.MRBC-reactive clone.

“…These autoantigens are revealed by treating mouse RBC with proteolytic en zymes such as bromelain [Cunliffe and Cox, 1979], The high background level of autoimmunity is not in creased by injections of mouse bromelain-treated (brom) RBC, but is increased by injecting mice with antilymphocyte serum or lipopolysaccharide (LPS). From these observations, Cunningham [1976] suggest ed that normally this autoimmune response is strong ly controlled, possibly by suppressor T cells.…”

Section: Introductionmentioning

confidence: 95%

“…Unimmunized mice contain a significant number of cells secreting IgM autoantibodies against antigens in the membranes of mouse red blood cells (RBC) [re viewed by Cunningham, 1976]. These autoantigens are revealed by treating mouse RBC with proteolytic en zymes such as bromelain [Cunliffe and Cox, 1979], The high background level of autoimmunity is not in creased by injections of mouse bromelain-treated (brom) RBC, but is increased by injecting mice with antilymphocyte serum or lipopolysaccharide (LPS).…”

Section: Introductionmentioning

confidence: 99%

Effects in Mice of Rat Bromelain-Treated RBC and Lipopolysaccharide on Autoantibody Production against Bromelain-Treated Isologous RBC

Ramos

et al. 1983

Autoantibody production against mouse bromelain-treated (brom) red blood cells (RBC) was significantly increased in mice injected with rat brom RBC. These autoantibodies were not adsorbed by rat brom RBC in serological assays and did not lyse rat brom RBC in plaque-forming cell (PFC) assays using mixtures of rat brom RBC and mouse brom RBC as targets. These data suggest that the increased response induced by rat brom RBC is not due to the presence of common, or similar, antigens on the two types of RBC. The spleens of mice injected with lipopolysaccharide (LPS), or with both LPS and rat brom RBC, had a markedly increased number of PFC lysing mouse brom RBC. About 20% of the PFC induced by LPS and rat brom RBC also lysed rat brom RBC. The autoimmune response was not increased in mice injected twice with rat brom RBC and the secondary response induced by two injections of LPS was lower than that induced by one injection of LPS. However, injection of LPS after an initial challenge with rat brom RBC induced an autoimmune response similar in size to that induced by LPS alone. The decreased secondary response against mouse brom RBC following a second injection of rat brom RBC was associated with decreased production of antibodies of various specificities as detected in a reverse PFC assay. These results do not support the hypothesis that the poor secondary responses against mouse brom RBC following a second injection of rat brom RBC are due to the exhaustive differentiation of autoimmune B cells as part of a fail-safe mechanism to prevent autoimmunity.