Population genetics of the heavy chain immunoglobulin allotypes in the rabbit.
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Biomedical subjects
Publications and source records attributed to S Dubiski.
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The structural basis for the A14 and A15 allotypic specificities of rabbit immunoglobulin G was investigated with Fe fragments prepared from homozygous rabbits. The presence of threonine in the Cgamma2 region (position 309: Eu numbering) correlates with the A14 allotype; the presence of alanine at this same position correlates with the A15. Now that the sequence of the Cgamma2 region of rabbit IgG has been completely elucidated, a high degree of homology of the constant region domains of rabbit and human gamma chains is apparent (about 60-80%).
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The injection into newborn rabbits of a small quantity of human albumin, associated with red blood corpuscles or nucleated rabbit cells, induces an antibody response in the majority of animals, whereas the same quantity of antigen in solution fails to stimulate antibody formation or induces tolerance. The promoting capacity of the cells depends on attachment of antigen to them. The antibody produced after the injection of albumin, associated with nucleated cells, is of recipient origin. However, immunoglobulin carrying the marker of donor cells can be demonstrated in the recipient animals, and may reach serum concentrations similar to those normally present in animals which are heterozygous with respect to the marker. It appears that the antibody-promoting function and the synthetic capacity for allotype are quite distinct and that the period required for allotype formation is very short with mononuclear peritoneal exudate cells and is very much longer with cells from the thymus. The capacity of cells from lymph nodes for sustained allotype formation is less than that of thymus cells but greater than that of mononuclear peritoneal exudate cells.
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Serum beta(IC) globulin, the third component of the complement system, was estimated by the single diffusion method (Oudin) and its significance in human glomerulonephritis was evaluated. This protein was depressed in two of three cases of acute proliferative glomerulonephritis and nine of 12 cases of acute glomerulonephritis. Beta(IC) globulin continued to be low in two cases of active subacute glomerulonephritis whereas it returned to normal in five of the cases of acute glomerulonephritis. Values were normal in eight patients with membranous glomerulonephritis, four with chronic glomerulonephritis and one with hereditary glomerulonephritis, as well as in patients with other renal diseases and diseases of non-renal origin. In addition, levels were elevated in six patients with diseases of possible immune pathogenesis. It is concluded that beta(IC) globulin estimation is a useful aid in the diagnosis and prognosis of glomerulonephritis in humans.
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The enhancement of the response of T cells to concanavalin A (ConA) and phtyohaemagglutinin (PHA) by macrophages has been shown in most species, whereas the accessory role of B cells has been only described in studies using human or rabbit lymphocytes. In rabbit, the accessory activity is confined to a subpopulation of B lymphocytes: the majority of B cells have sedimentation velocity of 2.5 to 4 mm/h, whereas the maximum of the accessory activity is found among the B cells, sedimenting with a velocity of 3.5 to 8 mm/h; B cells sedimenting between 1 and 3.5 mm/h have only a very weak accessory activity. Splenic adherent and/or phagocytic spleen cells may contribute additional augmentation of the response of T cells to ConA, since other macrophages (peritoneal and alveolar) are able to increase the ConA response to spleen T cells.