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<p>Genetic defects in <i>IL2RG</i> or <i>JAK3</i> can cause the phenotype of severe combined immunodeficiency (SCID) with absent T- and non-functional B-lymphocytes (T-B+ SCID). B cell function and the need for immunoglobulin replacement therapy after hematopoietic stem cell transplantation (HSCT) depends on the engraftment of donor B-lymphocytes. In a retrospective study we describe B-lymphocyte reconstitution after HSCT with the aim to identify B cell subpopulations as an early predictor for the maturation and function of B cells after HSCT. All patients included underwent HSCT in a single institution between 1980 and 2017. First, we studied B cell maturation in cryopreserved blood samples of 12 patients with B+ SCID (IL2RG-deficiency) after haploidentical HSCT presenting with mixed B cell chimerism. Recipient and donor B cell subpopulations were identified by HLA-staining using flow cytometry. In a consecutive step we compared B cell subpopulations irrespective of chimerism between patients with or without post-transplant B cell function. Samples for this study were obtained between day + 90 to + 250 after HSCT from 25 post-transplant long-term survivors with B-positive SCID (9 with genetic variants in <i>JAK3</i>, 16 in <i>IL2RG)</i>, 9/25 were dependent and 16/25 independent of immunoglobulin (Ig) -substitution.</p><p>We demonstrate that a proportion of less than 2% of donor B cells can be sufficient for posttransplant B cell function and that a proportion of more than 4.7% of switched memory (IgM-) B cells in the memory B cell population (CD19 + CD27+) between days + 90 and + 250 after HSCT correlates with normal B cell function and independence from immunoglobulin substitution.</p>

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Posttransplant B cell Development and Function in Patients with B cell Positive SCID Caused by Pathogenic Variants in IL2RG and JAK3

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年3月21日

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  • Eva-Maria Jacobsen,
  • Abdallah Khazaleh,
  • Kerstin Felgentreff,
  • Ingrid Furlan,
  • Katharina Wustrau,
  • Mehtap Sirin,
  • Holger Cario,
  • Benjamin Mayer,
  • Ulrich Pannicke,
  • Klaus Schwarz,
  • Klaus-Michael Debatin,
  • Wilhelm Friedrich,
  • Ansgar S. Schulz,
  • Manfred Hoenig

摘要

Genetic defects in IL2RG or JAK3 can cause the phenotype of severe combined immunodeficiency (SCID) with absent T- and non-functional B-lymphocytes (T-B+ SCID). B cell function and the need for immunoglobulin replacement therapy after hematopoietic stem cell transplantation (HSCT) depends on the engraftment of donor B-lymphocytes. In a retrospective study we describe B-lymphocyte reconstitution after HSCT with the aim to identify B cell subpopulations as an early predictor for the maturation and function of B cells after HSCT. All patients included underwent HSCT in a single institution between 1980 and 2017. First, we studied B cell maturation in cryopreserved blood samples of 12 patients with B+ SCID (IL2RG-deficiency) after haploidentical HSCT presenting with mixed B cell chimerism. Recipient and donor B cell subpopulations were identified by HLA-staining using flow cytometry. In a consecutive step we compared B cell subpopulations irrespective of chimerism between patients with or without post-transplant B cell function. Samples for this study were obtained between day + 90 to + 250 after HSCT from 25 post-transplant long-term survivors with B-positive SCID (9 with genetic variants in JAK3, 16 in IL2RG), 9/25 were dependent and 16/25 independent of immunoglobulin (Ig) -substitution.

We demonstrate that a proportion of less than 2% of donor B cells can be sufficient for posttransplant B cell function and that a proportion of more than 4.7% of switched memory (IgM-) B cells in the memory B cell population (CD19 + CD27+) between days + 90 and + 250 after HSCT correlates with normal B cell function and independence from immunoglobulin substitution.