PARTICIPATION OF UDP-GLC-GLUCOSILTRANSFERASE IN ASYMMETRIC ANTIBODIES SYNTHESIS

PRADOS MB, GENTILE T, MIRANDA S.

Córdoba, Argentina

Congreso; Latin American Congress of Immunology (ALAI); 2005

Asymmetric antibodies (AAb) constitute an irnportant factor in materno foetal tolerance. It has been demonstrated that its synthesis is regulated by IL-6 by means of UDP-glucoseglucosil transferase (GT). The airm of this work was to study GT activity and AAb production bv a murine hybridoma in the absence or presence of estrogens (E2) (10-7 y 10-8M) or progesterone (Pg) (10-5, 10-6, 10-9 and 10-10M) with or without anti/IL-6. Moreover, GT activity was analysed in peripheral blood B cells. B cells were obtained employing CD19 microbeads. Cell viability and purity were >90% as determined by FACS (cells analysed: CD3+/CD14+/CDI9+). GT activity was determined as the incorporation of 14C-Glc to denatured thyroglobulin. The AAb proportion was calculated by ELISA. Results show that Pg 10-6, 10-9 and 10-10 M diminished GT activity (-26±5%, -21±3% and -28±4%) and varied AAb proportion (-50±4%. 0±3% y +39±2%). The addition of anti/TL-6 inhibited the effects produced by Pg on GT activity and AAb production only when Pg concentration was 10-6M. Pg 10-5M increased GT activity (18±4%). E2 10-7M increased GT activity in a 22±5% not modifying AAb (0±5%), whereas E2 10-8M dirninished GT activity (-28±3%) and ÁAb (-62±3%), a value that was not modified by the addition nf anti/IL-6. B cells showed a GT activity between 0.92-l,5cpm/ug. This work shows that there is a dose dependent regulation of GT activity by E2 and Pg in vitro. Pg might modulate AAb production by two intracellular mechanisms: Pg 10-10 M has an stimulatory effect which does not depends on IL-6 and GT, whereas Pg 10-6 M has an inhibitory effect regulated by IL-6 and GT. The inhibitoy effect produced by E2 (10-8 M) might not depend on IL-6 and GT. Considering that there is a high GT expression in placenta and that Pg levels are around 10-5M at materno foetal interfase. these results suggest that GT might have a role in materno foetal tolerance.