Altered Modulation of the In Vitro Antibody Synthesis by Placental Factors from the CBA/J × DBA/2 Abortion-Prone Mating Combination

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Abstract
The in vitro immunomodulating effect of placental culture supernatants (PSs) obtained from two H-2k x H-2d allogeneic crossbreedings, the CBA/J x DBA/2 abortion-prone mating combination, and the reproductively normal pregnancy CBA/J x BALB/c crossbreeding were compared, and the influence of previous deliveries was evaluated. The behavior of placentae obtained from CBA/J females with two previous pregnancies by BALB/c males was also investigated. Supernatants of cultures of murine placentae were added to a mouse immunoglobulin (Ig) G1 hybridoma culture which produced anti-dinitrophenol (anti-DNP) antibodies. The quantity of monoclonal antibody produced, the nature of these antibodies, and the proliferation of the hybridoma cells were studied. CBA/J x DBA/2 placental factors obtained from multiparous females induced a diminished asymmetric IgG antibody production without varying the quantity of antibody produced. In contrast, PSs obtained from the nonresorption-prone CBA/J x BALB/c mating combination with the same number of previous deliveries enhanced the production of both symmetric and asymmetric anti-DNP molecules and also increased the proportion of asymmetric blocking monoclonal antibodies (mAbs) synthesized by the hybridoma. Both of the PSs analyzed had induced similar inhibition of 3H-thymidine uptake. PSs obtained from the abortion-prone mating combination whose CBA/J females had two previous pregnancies by BALB/c males showed similar immunomodulating effects to those observed using multiparous CBA/J x BALB/c placentae. We propose that the placenta produces soluble factors that participate in the regulation of antibody synthesis by the mother during gestation. Such a placental immunomodulating effect appears to be altered in the CBA/J x DBA/2 abortion-prone mating combination and could be corrected by previous pregnancies by BALB/c males. These observations suggest that placental factors would be relevant to the protection of the fetus and might play an important role in the immune equilibrium between mother and fetus. Asymmetric antibody production as a Th2 responsiveness was also discussed.