Journal of Clinical Immunology

, Volume 33, Issue 1, pp 96–110

Post-Transplantation B Cell Function in Different Molecular Types of SCID

  • Rebecca H. Buckley
  • Chan M. Win
  • Barry K. Moser
  • Roberta E. Parrott
  • Elisa Sajaroff
  • Marcella Sarzotti-Kelsoe
Original Research

Abstract

Purpose

Severe combined immunodeficiency (SCID) is a syndrome of diverse genetic cause characterized by profound deficiencies of T, B and sometimes NK cell function. Non-ablative HLA-identical or rigorously T cell-depleted haploidentical parental bone marrow transplantation (BMT) results in thymus-dependent genetically donor T cell development in the recipients, leading to a high rate of long-term survival. However, the development of B cell function has been more problematic. We report here results of analyses of B cell function in 125 SCID recipients prior to and long-term after non-ablative BMT, according to their molecular type.

Methods

Studies included blood immunoglobulin measurements; antibody titers to standard vaccines, blood group antigens and bacteriophage Φ X 174; flow cytometry to examine for markers of immaturity, memory, switched memory B cells and BAFF receptor expression; B cell chimerism; B cell spectratyping; and B cell proliferation.

Results

The results showed that B cell chimerism was not required for normal B cell function in IL7Rα-Def, ADA-Def and CD3-Def SCIDs. In X-linked-SCID, Jak3-Def SCID and those with V-D-J recombination defects, donor B cell chimerism was necessary for B cell function to develop.

Conclusion

The most important factor determining whether B cell function develops in SCID T cell chimeras is the underlying molecular defect. In some types, host B cells function normally. In those molecular types where host B cell function did not develop, donor B cell chimerism was necessary to achieve B cell function. 236 words

Keywords

B cell function B cell chimerism bone marrow transplantation severe combined immunodeficiency molecular type memory B cells 

Supplementary material

10875_2012_9797_MOESM1_ESM.docx (37 kb)
Supplemental Figure 1BAFF-R expression after transplantation. BAFF-R expression was tested by flow cytometry on CD19+ B cells in 56 PBMC samples from 27 SCID patients <12 years after BM transplantation, and in 15 control PBMC samples (14 individuals of ≥20 years of age and one newborn). (DOCX 37 kb)
10875_2012_9797_MOESM2_ESM.docx (439 kb)
Supplemental Fig. 2BCR Spectratype results from PBMC samples of an X-linked (X-1) (a), a Jak3-Def (J-2) (b), and an IL7Rα-Def (7–4) (c) SCID patients and a normal control (d). (DOCX 439 kb)

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Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Rebecca H. Buckley
    • 1
    • 2
  • Chan M. Win
    • 3
  • Barry K. Moser
    • 4
  • Roberta E. Parrott
    • 1
  • Elisa Sajaroff
    • 1
  • Marcella Sarzotti-Kelsoe
    • 2
    • 3
  1. 1.Department of PediatricsDuke University Medical CenterDurhamUSA
  2. 2.Department of ImmunologyDuke University Medical CenterDurhamUSA
  3. 3.Department of SurgeryDuke University Medical CenterDurhamUSA
  4. 4.Department of Biostatistics and BioinformaticsDuke University Medical CenterDurhamUSA

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