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

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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

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Acknowledgments

We thank the patients and their families, the physicians who referred them and who cared for them, Dr. A. Yu and D. Ozaki for their help with the BCR spectratype data, the members of the Duke University DNA Analysis Facility and the Duke Comprehensive Cancer Center Flow Cytometry Facility. This research was supported by National Institutes of Health grants AI47605 and AI042951, and in part by the Duke RBL (AI58607), and the Duke CTR (AI51445).

Disclosures: None of the authors has any commercial affiliations or consultancies to disclose.

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Authors and Affiliations

  1. Department of Pediatrics, Duke University Medical Center, Box 2898, 363 Jones Building, Durham, NC, 27710, USA

    Rebecca H. Buckley, Roberta E. Parrott & Elisa Sajaroff

  2. Department of Immunology, Duke University Medical Center, Durham, NC, 27710, USA

    Rebecca H. Buckley & Marcella Sarzotti-Kelsoe

  3. Department of Surgery, Duke University Medical Center, Durham, NC, 27710, USA

    Chan M. Win & Marcella Sarzotti-Kelsoe

  4. Department of Biostatistics and Bioinformatics, Duke University Medical Center, Durham, NC, 27710, USA

    Barry K. Moser

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  1. Rebecca H. Buckley
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  5. Elisa Sajaroff
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Correspondence to Rebecca H. Buckley.

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Supplemental Figure 1

BAFF-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)

Supplemental Fig. 2

BCR 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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Buckley, R.H., Win, C.M., Moser, B.K. et al. Post-Transplantation B Cell Function in Different Molecular Types of SCID. J Clin Immunol 33, 96–110 (2013). https://doi.org/10.1007/s10875-012-9797-6

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  • DOI: https://doi.org/10.1007/s10875-012-9797-6

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