Modulation of the immune response by progesterone-induced lymphocyte factors.

Rat spleen and peripheral blood lymphocytes express progesterone receptors whose concentration is increased greatly during the early phase of pregnancy. After stimulation of progesterone the expression of receptors was augmented 2-3 times. When cells were cultured in the presence of progesterone they released a soluble factor that inhibited cellular immunoreactions (MLR, CRC) and cellular proliferation as measured by thymidine incorporation by spleen-cell culture. This factor also inhibited the synthesis of anti-DNP antibodies by a mouse hybridoma and diminished the proportion of cells in phase S. However, the percentage of asymmetric molecules produced by the hybridoma remained unaltered. These results support the hypothesis that soluble factors released by rat lymphocytes modulate the immune response of the mother and participate in the mechanism that protects the fetus against antipaternal antibodies.

Asymmetric non-precipitating antibodies in commercial hyperimmune gamma-globulin for therapeutic use.

The presence of asymmetric (non-precipitating or co-precipitating) antibodies has been studied in three commercial preparations of antitetanus gamma-globulin. It was found that 27% of the specific antibodies are of asymmetric type, a value two to three times higher than that found in normal IgG. In toxicity tests in mice with tetanus toxin, the asymmetric antibodies were 2.7 times less effective than the symmetric ones. It is concluded that the protection capacity of the tetanus gamma-globulin preparations is dependent on the ratio of symmetric to asymmetric antibodies. The high content of asymmetric antibodies is probably due to the fact that immunization is performed with the antigen in a particulate form.

IgG asymmetric molecules with antipaternal activity isolated from sera and placenta of pregnant human.

The proportion of symmetric and asymmetric IgG molecules was studied in 10 mothers at delivery. IgG was obtained from peripheral blood and placental blood sera and by elution at 4 M KCl from placenta cell membranes. The percentage of symmetric and asymmetric molecules was determined in the IgG and in their corresponding F(ab')2 fragments by absorption to Con A-Sepharose. The presence of antipaternal antibodies was investigated by IIF and MC tests using paternal lymphocytes. The average percentage of asymetric IgG molecules in the sera was 24.4, which is about double the value of that found in normal subjects. In the IgG eluted from the placenta, the proportion of asymmetric IgG was much higher, averaging 44.4%. Antipaternal antibodies were detected in 5 mothers by IIF and MC and in two mothers only by IIF. In three mothers no antibodies could be detected. It was found that the concentration of antipaternal antibodies was about three times higher in the asymmetric IgG fraction than in the summetric one. Considering the percentage of asymmetric IgG molecules with antipaternal antigen specificity eluted from placenta and the possibility that they function as blocking antibodies, their participation in fetal protection is suggested.

Asymmetric Fab glycosylation in guinea-pig IgG1 and IgG2.

The presence of asymmetric antibody molecules has been investigated in both IgG1 and IgG2 subclasses of guinea-pig immunoglobulins. It was found that about 20% of the IgG1 and 10% of the IgG2 were of asymmetric type. The proportion was essentially the same in the sera of normal animals, animals hyperimmunized with dinitrophenyl-bovine gamma globulin (DNP-BGG) and Freund's adjuvant, and animals infected with Trichinella spiralis. In the case of animals immunized with DNP-BGG, no differences were observed in the proportion of asymmetric molecules between the specific antibodies and the IgG not specific for the immunizing antigen. It is concluded that the asymmetric glycosylation occurs to a different extent in each subclass and that it is not affected by the antigen specificity of the antibodies studied.

Asymmetrically glycosylated IgG isolated from non-immune human sera.

When human IgG or its F(ab')2 fragment purified from a pool of non-immune sera was passed through a Con A-Sepharose column, 12% of the molecules bound to concanavalin A. While 44% of Fab' and 72% of Fd' fragments obtained from F(ab')2 retained by concanavalin A and eluted with methyl alpha-D-mannoside bound to concanavalin A, the Fab' and Fd' fragments obtained from non-retained F(ab')2 and the L chains and Fc fragments did not interact with the lectin. Only Fd' fragment obtained from the F(ab')2 retained by concanavalin A inhibited the fixation of guinea-pig erythrocytes to concanavalin A. These results are similar to those previously observed for IgG antibodies of different animal species and indicate that partial asymmetric glycosylation is a general phenomenon that is not restricted exclusively to IgG molecules with known specificity.