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* Department of Pediatrics and
Department of Gynecology, Philipps University Marburg, Marburg, Germany;
Department of Pediatrics, Charité Berlin, Campus Virchow, Berlin, Germany;
Department of Pathology, Charité Berlin, Campus Benjamin Franklin, Berlin, Germany;
¶ Deutsches Rheumaforschungszentrum, Berlin, Germany; and
|| Department of Pediatrics, Johann Wolfgang Goethe University, Frankfurt, Germany
During the perinatal period the development of the IgH chain CDR3 (CDR-H3) repertoire of IgM transcripts is maturity-dependent and not influenced by premature exposure to Ag. To study whether maturity-dependent restrictions also predominate in the perinatal IgG repertoire we compared 1000 IgG transcripts from cord blood and venous blood of extremely preterm neonates (24–28 wk of gestation) and of term neonates from birth until early infancy with those of adults. We found the following. First, premature contact with the extrauterine environment induced the premature development of an IgG repertoire. However after preterm birth the diversification of the IgG repertoire was slower than that after term birth. Second, the IgG repertoire of preterm neonates retained immature characteristics such as short CDR-H3 regions and overrepresentation of DH7–27. Third, despite premature exposure to the extrauterine environment, somatic mutation frequency in IgG transcripts of preterm infants remained low until they reached a postconceptional age corresponding to the end of term gestation. Thereafter, somatic mutations accumulated with age at similar rates in preterm and term neonates and reached 30% of the adult level after 6 mo. In conclusion, class switch was inducible already at the beginning of the third trimester of gestation, but the developing IgG repertoire was characterized by similar restrictions as those of the developing IgM repertoire. Those B cells expressing more "mature" H chain sequences were not preferentially selected into the IgG repertoire. Therefore, the postnatal IgG repertoire of preterm infants until the expected date of delivery differs from the postnatal repertoire of term neonates.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported in part by Deutsche Forschungsgemeinschaft Grants BA1187/6-1 (to K.B. and M.Z.), SFB/TR22, TPA17 (to M.Z.), and the Humboldt Foundation Fellowship Grant FLF1071857 (to M.Z.). The Deutsches Rheumaforschungszentrum is supported by the Berlin Senate of Research and Education.
2 Address correspondence and reprint requests to Dr. Michael Zemlin, Department of Pediatrics, Philipps University Marburg, Baldinger Street, 35033 Marburg, Germany. E-mail address: zemlin{at}staff.uni-marburg.de
3 Abbreviation used in this paper: FR, framework region.
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