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Survival of the fetus: fetal B and T cell receptor repertoire development

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Abstract

A mature and diverse T and B cell receptor repertoire is a prerequisite for immunocompetence. In light of its increased susceptibility to infection, the human fetus has long been considered deficient in this regard. However, data accumulated since the 1990s and in earnest in the past couple of years paints a more complicated picture. As we describe in this review, mechanisms responsible for generating a diverse receptor repertoire, such as somatic recombination, class switch recombination, and somatic hypermutation, are all operational to surprising extents in the growing fetus. The composition of the fetal repertoire differs from that of adults, with preferential usage of certain variable (V), diversity (D), and joining (J) gene segments and a shorter complementarity determining (CDR3) region, primarily due to decreased terminal deoxynucleotidyl transferase (TdT) expression. Both T and B cell receptor repertoires are extremely diverse by the end of the second trimester, and in the case of T cells, are capable of responding to an invading pathogen with in utero clonal expansion. Thus, it would appear as though the T and B cell receptor repertoires are not a hindrance towards immunocompetence of the newborn. Our improved understanding of fetal receptor repertoire development is already bearing fruit in the early diagnosis of primary immunodeficiencies (PID) and may help clarify the pathogenesis of congenital infections, recurrent abortions, and autoimmune disorders in the near future.

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Acknowledgments

Raz Somech is supported by the Jeffrey Modell Foundation (JMF). This review and some of the work were performed in partial fulfillment of the requirements of the PhD of Erez Rechavi at the Sackler School of Medicine (Tel Aviv University).

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Authors and Affiliations

  1. Pediatric Department A and Immunology Service, Jeffrey Modell Foundation Center, “Edmond and Lily Safra” Children’s Hospital, Sheba Medical Center, Tel Hashomer, Sackler School of Medicine, Tel Aviv University, 6997801, Tel Aviv, Israel

    Erez Rechavi & Raz Somech

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  1. Erez Rechavi
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  2. Raz Somech
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Correspondence to Raz Somech.

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This article is a contribution to the special issue on Immunocompetence of the Newborn -- Guest Editors: Arnaud Marchant and Tobias Kollmann

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Rechavi, E., Somech, R. Survival of the fetus: fetal B and T cell receptor repertoire development. Semin Immunopathol 39, 577–583 (2017). https://doi.org/10.1007/s00281-017-0626-0

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  • DOI: https://doi.org/10.1007/s00281-017-0626-0

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