Research Article: Decreased production of class-switched antibodies in neonatal B cells is associated with increased expression of miR-181b

Date Published: February 1, 2018

Publisher: Public Library of Science

Author(s): Stephanie Glaesener, Christine Jaenke, Anika Habener, Robert Geffers, Petra Hagendorff, Katrin Witzlau, Esther Imelmann, Andreas Krueger, Almut Meyer-Bahlburg, Menno C van Zelm.

http://doi.org/10.1371/journal.pone.0192230

Abstract

The increased susceptibility to infections of neonates is caused by an immaturity of the immune system as a result of both qualitative and quantitative differences between neonatal and adult immune cells. With respect to B cells, neonatal antibody responses are known to be decreased. Accountable for this is an altered composition of the neonatal B cell compartment towards more immature B cells. However, it remains unclear whether the functionality of individual neonatal B cell subsets is altered as well. In the current study we therefore compared phenotypical and functional characteristics of corresponding neonatal and adult B cell subpopulations. No phenotypic differences could be identified with the exception of higher IgM expression in neonatal B cells. Functional analysis revealed differences in proliferation, survival, and B cell receptor signaling. Most importantly, neonatal B cells showed severely impaired class-switch recombination (CSR) to IgG and IgA. This was associated with increased expression of miR-181b in neonatal B cells. Deficiency of miR-181b resulted in increased CSR. With this, our results highlight intrinsic differences that contribute to weaker B cell antibody responses in newborns.

Partial Text

The immaturity of the developing immune system in early life is reflected by an increased susceptibility to infections and decreased vaccination responses. Multiple factors within the innate and adaptive arm of the immune system have been identified contributing to this immaturity. Regarding humoral immunity, the neonate is initially protected by passively acquired maternal antibodies, although neonates are able to mount T cell-dependent and—independent immune responses [1–3]. However, neonatal antibody responses are delayed in onset, show decreased peak levels, are of shorter duration, and of lower antibody affinity [3–5]. The generation of high-affinity, class-switched, antibodies is a complex process relying on the interaction of T-, B-, and antigen-presenting cells (APCs). Thus, the immaturity of the neonatal immune system results from quantitative and qualitative deficiencies of many different cell types and their interplay with each other.

The immaturity of the neonatal immune system is a result of both qualitative and quantitative differences between neonatal and adult immune cells. In respect to the B cell compartment several studies have demonstrated an altered composition of B cell subpopulations [16, 18] in addition to functional differences [7, 8, 24, 25]. However, because of their different subset composition, comparisons between adult and neonatal total B cells might give misleading information. In the current study we therefore directly compared corresponding human B cell subpopulations from neonatal CB and peripheral AB, namely T1, T2 and naïve mature B cells gated as previously described [43–45]. Notably, we did not separate and analyze T3 B cells which can be separated from CD24intCD38int naïve mature B cells by differential expression of the ABCB1 transporter [46]. In cord blood, a higher proportion is contained within CD24intCD38int naïve mature B cells compared to adult peripheral blood. However, no differences in calcium flux or proliferation between naïve mature and T3 B cells have been observed and other functional data including Ig production have not been described so far. Therefore, we did not include this subset in our analysis.

 

Source:

http://doi.org/10.1371/journal.pone.0192230

 

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