Effect of genetic type of SCID on T, B, and NK cell function following bone marrow stem cell transplantation

Journal Article

The purpose of this study was to evaluate the effect of a mutated microenvironment on the development of T, B and NK cell function in 62 SCIDs following non-ablative T cell-depleted bone marrow stem cell transplantion. 34 SCIDs were γc-deficient, 10 were ADA-deficient, 5 were Jak3-deficient, 11 were autosomal recessive and 2 were of unknown type. Normal T cell function developed(all donor T cells) in all 62 chimeras. However, B cell function remained abnormal in 33, and only 21 had some donor B cells. A majority of the γc-deficient and Jak3-deficient SCIDs had poor B cell function, as demonstrated by failure of isotype-switching following immunization with φX 174, whereas a majority of the ADA-deficient and autosomal recessive SCIDs had good B cell function. Prior to engraftment, a high percentage of B cells in all SCIDs expressed CD1a, CD10, CD5 and CD38; however, γc-deficient and Jak3-deficient B cells had the highest expression of CD1a and the lowest expression of CD38, while B cells from ADA-deficient and autosomal recessive SCIDs had the highest expression of CD38. Post-transplantation, B cell CD1a remained high, CD10 and CD38 declined, and CD5 expression increased. Prior to engraftment, NK cell numbers and function were lowest in γc-deficient and Jak3-deficient SCIDs, whereas they were higher than normal in all other types. Following transplantation, γc- and Jak3-deficients continued to have profoundly low NK numbers and function, while these normalized in all other types. Thus, stem cells that mature in a microenvironment where γc and Jak3 are mutated fail to mature into normal B or NK cells, despite the development of normal T cells and T cell function.

Duke Authors

Cited Authors

  • Buckley, RH

Published Date

  • March 20, 1998

Published In

Volume / Issue

  • 12 / 5

International Standard Serial Number (ISSN)

  • 0892-6638

Citation Source

  • Scopus