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Biomedical subjects

M W Steward

Publications and source records attributed to M W Steward.

At least 127 records · Page 7Linked to original sources

Evidence for the genetic control of antibody affinity from breeding studies with inbred mouse strains producing high and low affinity antibody.

The amount (Abt) and relative affinity (KR) of antibody produced in response to protein antigens injected in saline has been measured in the parents, F1 hybrids and backcross offspring of inbred mice which produce high and low KR antibody to these antigens. The results obtained support the view that antibody affinity is under polygenic control. Furthermore, strain related variation in Abt is independent of KR and the breeding experiments indicate that these two parameters are under independent genetic control.

Animals↗

Macrophage clearance function and immune complex disease in New Zealand Black/White F1 hybrid mice.

Macrophage clearance function in NZB, NZW, NZB/W, Ajax and B10D2 new mice was assessed by measurement of the rate of clearance (KPVP) of intravenously-injected 125I-labelled polyvinylpyrrolidone (PVP). There were significant strain and age-related variations in KPVP. In particular there was a marked fall in KPVP in NZB/W mice with increasing age. This fall was most apparent in female NZB/W and preceded the age at which renal disease usually develops in these animals. We suggest that ineffective macrophage function and production of low affinity antibody contribute to the early development of immune complex glomerulonephritis in these mice.

Age Factors↗

Studies on the genetic control of antibody affinity: the independent control of antibody levels and affinity in Biozzi mice.

The levels (Abt) and relative affinity (KR) of antibody produced to protein antigens injected in saline have been measured in the 22nd generation of the Biozzi high (Ab/H) and low (Ab/L) antibody-producing mice. No significant differences in affinity were observed between the two lines of mice (p 0.10) but the levels of antibody (Abt) differed significantly (p 0.0025) when immunized with antigen in saline; however, both Ab/H and Ab/L mice were able to mount a high affinity response to protein antigens injected in Freund's complete adjuvant. These results substantiate earlier observations that in mice, antibody affinity (KR) and antibody level (Abt) are under independent genetic control.

Animals↗

Changes in immunoglobulin class and subclass of anti-DNA antibodies with increasing age in N/ZBW F1 hybrid mice.

The immunoglobulin class and subclass distribution of antibodies to double-stranded (ds) DNA has been determined in NZB/W F1 hybrid mice by a double antibody radioimmunoassay. The results show that there are marked age- and sex-related variations in the class and subclass distribution of these antibodies. In young mice of both sexes, the predominant anti-ds DNA antibody was of the IgM class, but as the animals aged, there was an increase in the level of the IgG2a and IgG2b antibodies. An apparent switch from predominantly IgM to IgG antibody occurred in females before males and at about the age of onset of overt immune complex disease in these animals. The possible significance of these results in the pathogenesis of the murine lupus syndrome is discussed.

Aging↗

The genetic control of antibody affinity in mice.

Random-bred TO mice have been selectively bred into two lines on the basis of the relative affinity (KR) of antibody produced to protein antigens, one line producing high and the other low KR antibody. After four generations of selective breeding the difference in KR between the two lines was highly significant (P less than 0-001). The selection on the basis of KR did not result in a corresponding selection for antibody levels (Abt), which were not significantly different in the two lines. These results indicate that antibody affinity is a genetically controlled parameter of the immune response. Furthermore, this control appears to be expressed by a mechanism which is independent of the amount of antibody produced.

Animals↗

The role of low affinity antibody in immune complex disease. The quantity of anti-DNA antibodies in NZB/W F1 hybrid mice.

The level and avidity of anti-DNA antibody in the serum of New Zealand Black/White (NZB/W F1) hybrid mice has been determined. The results show that there is an age and sex-related variation in the avidity of this antibody. In mice of both sexes, the avidity of circulating anti-DNA antibody increases up to 5 months of age; thereafter the avidity falls with increasing age. These variations are more marked in males, but female mice consistently have lower avidity anti-DNA antibody than males. Thus the time of onset, time course and severity of the murine lupus syndrome in NZB/W F1 mice are associated with the presence of increasing levels of low avidity anti-DNA antibody in the serum. These results are discussed in the context of the possible role of low avidity antibody in immune complex disease.

Aging↗