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

Version 1

      Publication Details (including relevant citation   information):

      Rogosch T, Kerzel S, Hoss K, Hoersch G, Zemlin C, Heckmann M,   Berek C, Schroeder HW Jr, Maier RF, Zemlin M.

      J Immunol.   2012 Dec 1;189(11):5449-56.

      doi: 10.4049/jimmunol.1103347

      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.

      Address (URL): http://www.ncbi.nlm.nih.gov/pubmed/23105134