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Affinity-Dependent Alterations of Mouse B Cell Development by Noninherited Maternal Antigen¹

Laboratory of Immune Regulations and Development,⁴ Department of Developmental Biology, and Flow Cytometry Unit,⁵ J. Monod Institute, UMR 7592 (CNRS and Universities Paris 6 and 7), 75251 Paris cedex 05, France

We have examined the passage of maternal cells into the fetus during the gestation and postpartum in mice. Using enhanced green fluorescent protein (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 noninherited H-2K^k or H-2K^b maternal antigens (NIMA) during gestation and lactation was compared with those of nonexposed controls. In H-2K^k-exposed fetuses, NIMA-specific transgenic B cells are partially deleted during late gestation. Nondeleted cells have downmodulated their B cell receptor. In contrast, in NIMA H-2K^b-exposed neonates, transgenic B cells present an activated phenotype, including proliferation, upregulation 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 wk of age. Thus, we show that fetal and neonatal B cell development is affected by maternal cells bearing antigens noninherited by the fetus and that this phenomenon is highly dependent on the affinity of the B cell receptor for the NIMA.

¹ Supported by the Ministère de l'Education Nationale, de la Recherche et de la Technologie and the Association pour la Recherche contre le Cancer. S.M.C. was supported by the Fondation pour la Recherche Médicale and the Ligue Nationale contre le Cancer.

² Correspondence: Colette Kanellopoulos-Langevin, Laboratory of Immune Regulations and Development, J. Monod Institute, Tour 43, 2 place Jussieu, 75251 Paris cedex 05, France. FAX: 33 1 44275265;kanellopoulos{at}ijm.jussieu.fr

³ Current address: National Institute of Health, Bethesda, MD 20892

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