Affinity-dependent alterations of mouse B cell development by noninherited maternal antigen.
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 mu/delta transgenic mouse model, whose B cells recognize the major histocompatibility complex class I molecules H-2Kk and H-2Kb, with a high or moderate affinity, respectively. The fate of transgenic B cells in animals exposed to noninherited H-2Kk or H-2Kb maternal antigens (NIMA) during gestation and lactation was compared with those of nonexposed controls. In H-2Kk-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-2Kb-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.
Laboratory of Immune Regulations and Development, J Monod Institute, Paris, France.
Cécile
C
Vernochet
Stéphane M
SM
Caucheteux
Marie-Claude
MC
Gendron
Josiane
J
Wantyghem
Colette
C
Kanellopoulos-Langevin
D000818:Animals; D000831:Animals, Newborn; D001402:B-Lymphocytes / Q000201:enzymology / Q000378:metabolism / Q000502:physiology*; D001973:Bromodeoxyuridine; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D005805:Genes, MHC Class I / Q000502:physiology*; D005865:Gestational Age; D049452:Green Fluorescent Proteins / Q000235:genetics; D006183:H-2 Antigens / Q000502:physiology*; D008431:Maternal-Fetal Exchange / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010641:Phenotype; D011247:Pregnancy; D011946:Receptors, Antigen / Q000096:biosynthesis / Q000235:genetics; D013601:T-Lymphocytes / Q000201:enzymology / Q000502:physiology
D006183:H-2 Antigens; C032876:H-2Kb protein, mouse; D011946:Receptors, Antigen; D049452:Green Fluorescent Proteins; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases; D001973:Bromodeoxyuridine