A progesterone-induced protein increases the synthesis of asymmetric antibodies

K. Kelemen, I. Bognar, M. Paal, J. Szekeres-Bartho

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Abstract

The immunological effects of progesterone are mediated, by a 34-kDa protein named the progesterone-induced blocking factor (PIBF). PIBF induces increased production of Th2-type cytokines; thus, it might stimulate antibody synthesis by B cells. There is a population of antibodies which, owing to the presence of a mannose-rich oligosaccharide residue on one of the Fab arms of the molecule, possess an asymmetric structure. Due to the asymmetric structure these molecules have no effector functions; however, they might act as blocking antibodies. This study was aimed at investigating the effect of progesterone-dependent immunomodulation on antibody production by B cells, with special emphasis on the synthesis of asymmetric nonprecipitating antibodies. The ratio of asymmetric IgG was significantly higher in supernatants of hybridoma cells cultured in the presence of PIBF than in those cultured in the absence of PIBF. Lymphocytes from healthy pregnant women produce significantly more PIBF than those of women with pathological pregnancies. The present studies revealed a positive relationship between asymmetric antibody content of the sera and PIBF expression on lymphocytes. Blocking of progesterone receptors by RU 486 or neutralizing endogenous PIBF activity by specific antibody significantly reduced the production of asymmetric antibodies in pregnant mice. Effector function of conventional and asymmetric antibodies was compared in a TNFα neutralization assay. Purified asymmetric anti-TNFα antibodies did not neutralize the cytotoxic effect of TNFα on L929 murine fibroblast target cells, whereas conventional anti-TNFα antibodies in the same concentration significantly (P < 0.001) reduced cytotoxicity. Our data suggest that PIBF induces increased production of asymmetric antibodies. These antibodies fail to exhibit effector functions and by blocking fetally derived antigens might contribute to protection of the fetus.

Original languageEnglish
Pages (from-to)129-134
Number of pages6
JournalCellular Immunology
Volume167
Issue number1
DOIs
Publication statusPublished - Jan 10 1996

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ASJC Scopus subject areas

  • Immunology

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