The Postnatal Maturation of the Immunoglobulin Heavy Chain IgG Repertoire in Human Preterm Neonates Is Slower than in Term Neonates

Abstract

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.

Evidence of Impact of Maternal HIV Infection on Immunoglobulin Levels in HIV-Exposed Uninfected Children

“…The models were adjusted for gender, race, and prematurity and associations with IgG, IgM, and IgA were similar to data described by others such as lower IgG early in life in premature compared to term children and higher IgG in black compared to white children (data not shown). [19][20][21][22] Maternal IgG is associated with Ig levels in children born to HIV-infected mothers…”

“…19 The study showed results similar to the previously reported associations between immunoglobulin levels and prematurity, gender, race, and maternal injecting drug use. [20][21][22][23] In the first 6 months of life the higher levels of IgG in uninfected children born to HIV-infected women can be explained by the higher maternal antibody titers in HIV-infected mothers compared to HCV-infected mothers. 24,25 However, the higher IgG levels in HIV-uninfected children persisted up to at least 24 months of age, when no maternal IgG remains.…”

A Population of CD19highCD45R−/lowCD21low B Lymphocytes Poised for Spontaneous Secretion of IgG and IgA Antibodies

“…Alternatively, IgG/IgA-secreting CD19 high CD45R Ϫ/low spleen cells could be a physiological correlate of the distinct developmental pathway to IgG-and IgA-switched B cells described in Ig-deficient mice, which is established at the level of B cell precursors and is T independent (43,44). Although not induced by intentional immunization, the IgG/IgA production of the CD19 high CD45R Ϫ/low B cells might be the result of regular microbial encounters (45), particularly, intestinal bacteria, but these cells also contributed importantly to the early postnatal IgG production, which is known to be developmentally controlled and (foreign) Ag independent (46). All together, the enrichment in Igsecreting plasma cells, the extrafollicular location, and the negative/low expressions of CD45R and CD21 surface BCR coreceptors suggest a relationship of the splenic CD19 high CD45R…”

Synchronous Recurrence of Group B Streptococcal Late-Onset Sepsis in Twins

“…12 Most likely contributive to this risk are alterations of the adaptive immune system, such as decreased immunoglobulin G levels and a slower maturation of the V H gene repertoire in premature infants. 13 The idea that young infants in general may be exquisitely sensitive to small GBS inocula, for example, in breast milk, is supported by a GBS sepsis model in neonatal mice, in which subcutaneous injection of 15 bacteria was lethal for 20% of the challenged mice. 14 Furthermore, 60% to 70% of preweaned mice (15-21 days old) succumbed to an enteral infection with HvgA-expressing GBS, whereas mice $4 weeks are protected.…”