Immunology

Affinity-Dependent Alterations of Mouse B Cell Development by Non-Inherited Maternal Antigen

Abstract
We have examined the passage of maternal cells into the fetus during the gestation and post-partum in mice. Using EGFP-transgenic females, we showed that maternal cells frequently gain access to the fetus, mostly in syngeneic pregnancies, but also in allogeneic and outbred crosses. EGFP-transgenic cells, including B, T and Natural Killer cells, can persist until adulthood, primarily in bone marrow and thymus. We then asked whether maternal cells, bearing antigens not inherited by the fetus, influence the development of fetal and neonatal B lymphocytes. We have used the B cell receptor 3-83 µ transgenic mouse model whose B cells recognize the Major Histocompatibility Complex class I molecules H-2K^k and H-2K^b, with a high or moderate affinity, respectively. The fate of transgenic B cells in animals exposed to non-inherited H-2K^k or H-2K^b maternal antigens (NIMA) during gestation and lactation was compared to those of non-exposed controls. In H-2K^k-exposed fetuses, NIMA-specific transgenic B cells are partially deleted during late gestation. Non-deleted cells have down-modulated their B cell receptor. In contrast, in NIMA H-2K^b-exposed neonates, transgenic B cells present an activated phenotype, including proliferation, up-regulation of surface CD69 and preferential localization in the T cell zone of splenic follicles. This state of activation is still clearly detectable up to 3 weeks of age. Thus, we show that fetal and neonatal B cell development is affected by maternal cells bearing antigens non inherited by the fetus and that this phenomenon is highly dependent on the affinity of the B cell receptor for the NIMA.

Key words: Embryo • Immunology • Pregnancy • Developmental biology

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