EFFECT OF PREGNANCY AND PLACENTAL FACTORS ON THE QUALITY OF HUMORAL IMMUNE-RESPONSE

Asymmetrical IgG molecules are characterised by the presence of a mann ose-rich oligosaccharide group in only one of the two Fab fragments, w hich impairs the corresponding paratope, causing such molecules to beh ave as univalent antibodies and therefore as antigen blockers [1-3]. D uring human and murine pregnancy, an increase has been detected in asy mmetrical IgG molecules in serum and those bound to the placenta, whic h normally releases factors capable of modulating the immune response. It thus seemed of interest to investigate the effect of placental cul ture supernatants (PCS) on in vivo and in vitro synthesis of rat immun oglobulin IgG(1), IgG(2a), IgG(2b) and IgG(2c), particularly the ratio of symmetrical and asymmetrical molecules in each isotype. The effect of PCS was determined in vivo by means of passive transfer to virgin females and in vitro by analysing the supernatants of spleen cells cul tured in the presence of PCS. The results showed that neither pregnanc y status nor PCS were capable of modifying serum levels of IgG(2a), Ig G(2b) or IgG(2c), whereas the level of IgG(1) was reduced. When PCS we re added to the spleen cells cultures, an in vitro increase was observ ed in IgG(2a), IgG(2b) and IgG(2c) production. The separation of symme trical from asymmetrical IgG molecules was performed by affinity chrom atography in Concanavalin A-Sepharose, as such lectin binds high manno se sugars present only in asymmetrical IgG molecules. It is shown that pregnancy and PCS induce an increase in IgG(1) and IgG(2) molecules a symmetrically glycosylated, capable of binding to ConA-Sepharose. Ther efore, the placenta is capable of releasing factors which can regulate the relative proportion of asymmetrical IgG molecules and induce quan titative and qualitative modifications of the in vitro and in vivo pro duced antibodies. (C) 1998 Elsevier Science B.V. All rights reserved.