B-cell differentiation and IL-21 response in IL2RG/JAK3 SCID patients after hematopoietic stem cell transplantation Journal Article


Authors: Miggelbrink, A. M.; Logan, B. R.; Buckley, R. H.; Parrott, R. E.; Dvorak, C. C.; Kapoor, N.; Abdel-Azim, H.; Prockop, S. E.; Shyr, D.; Decaluwe, H.; Hanson, I. C.; Gillio, A.; Dávila Saldaña, B. J.; Eibel, H.; Hopkins, G.; Walter, J. E.; Whangbo, J. S.; Kohn, D. B.; Puck, J. M.; Cowan, M. J.; Griffith, L. M.; Haddad, E.; O’Reilly, R. J.; Notarangelo, L. D.; Pai, S. Y.
Article Title: B-cell differentiation and IL-21 response in IL2RG/JAK3 SCID patients after hematopoietic stem cell transplantation
Abstract: Allogeneic hematopoietic stem cell transplant (HSCT) typically results in donor T-cell engraftment and function in patients with severe combined immunodeficiency (SCID), but humoral immunity, particularly when using donors other than matched siblings, is variable. B-cell function after HSCT for SCID depends on the genetic cause, the use of pre-HSCT conditioning, and whether donor B-cell chimerism is achieved. Patients with defects in IL2RG or JAK3 undergoing HSCT without conditioning often have poor B-cell function post-HSCT, perhaps as a result of impairment of IL-21 signaling in host-derived B cells. To investigate the effect of pre-HSCT conditioning on B-cell function, and the relationship of in vitro B-cell function to clinical humoral immune status, we analyzed 48 patients with IL2RG/ JAK3 SCID who were older than 2 years after HSCT with donors other than matched siblings. T follicular helper cells (TFH) developed in these patients with kinetics similar to healthy young children; thus, poor B-cell function could not be attributed to a failure of TFH development. In vitro differentiation of B cells into plasmablasts and immunoglobulin secretion in response to IL-21 strongly correlated with the use of conditioning, donor B-cell engraftment, freedom from immunoglobulin replacement, and response to tetanus vaccine. Patients receiving immunoglobulin replacement who had normal serum immunoglobulin M showed poor response to IL-21 in vitro, similar to those with low serum IgM. In vitro response of B cells to IL-21 may predict clinically relevant humoral immune function in patients with IL2RG/JAK3 SCID after HSCT. Copyright 2011 by The American Society of Hematology; all rights reserved.
Journal Title: Blood
Volume: 131
Issue: 26
ISSN: 0006-4971
Publisher: American Society of Hematology  
Date Published: 2018-06-28
Start Page: 2967
End Page: 2977
Language: English
DOI: 10.1182/blood-2017-10-809822
PROVIDER: scopus
PMCID: PMC6024640
PUBMED: 29728406
DOI/URL:
Notes: Article -- Export Date: 1 August 2018 -- Source: Scopus
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MSK Authors
  1. Susan E Prockop
    159 Prockop
  2. Richard O'Reilly
    460 O'Reilly