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IgA response in preterm neonates shows little evidence of antigen-driven selection.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Zemlin, Michael Maier, Rolf F. Kerzel, Sebastian Rogosch, Tobias Hoersch, Gabriele Heckmann, Matthias Hoss, Katharina Zemlin, Cosima Berek, Claudia Schroeder, Harry W.
Description	Country affiliation: Germany Author Affiliation: Rogosch T ( Department of Pediatrics, Philipps University Marburg, 35033 Marburg, Germany.)
Abstract	After birth, contact to environmental Ags induces the production of IgA, which represents a first line of defense for the neonate. We sought to characterize the maturation of the repertoire of IgA H chain transcripts in circulating blood B cells during human ontogeny. We found that IgA H chain transcripts were present in cord blood as early as 27 wk of gestation and that the restrictions of the primary Ab repertoire (IgM) persisted in the IgA repertoire. Thus, B cells harboring more 'mature' V(H) regions were not preferred for class switch to IgA. Preterm and term neonates expressed a unique IgA repertoire, which was characterized by short CDR-H3 regions, preference of the J(H) proximal D(H)7-27 gene segment, and very few somatic mutations. During the first postnatal months, these restrictions were slowly released. Preterm birth did not measurably accelerate the maturation of the IgA repertoire. At a postconceptional age of 60 wk, somatic mutation frequency of IgA H chain transcripts reached 25% of the adult values but still showed little evidence of Ag-driven selection. These results indicate that similar to IgG, the IgA repertoire expands in a controlled manner after birth. Thus, the IgA repertoire of the newborn has distinctive characteristics that differ from the adult IgA repertoire. These observations might explain the lower affinity and specificity of neonatal IgA Abs, which could contribute to a higher susceptibility to infections and altered responses to vaccinations, but might also prevent the development of autoimmune and allergic diseases.
ISSN	00221767
e-ISSN	15506606
DOI	10.4049/jimmunol.1103347
Journal	The Journal of Immunology
Issue Number	11
Volume Number	189
Language	English
Publisher	The American Association of Immunologists
Publisher Date	2012-12-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Antigens Immunology B-lymphocytes Gene Expression Regulation, Developmental Immunoglobulin A Genetics Immunoglobulin Heavy Chains Rna, Messenger Antibody Affinity Antibody Diversity Antibody Specificity Metabolism Fetal Blood Gestational Age Immunity, Innate Immunoglobulin Class Switching Immunoglobulin M Immunoglobulin Variable Region Infant Infant, Newborn Infant, Premature Molecular Sequence Data Biosynthesis Research Support, Non-u.s. Gov't Discipline Immunology
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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