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

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 Scholars

Author Rebecca Hatcher Buckley Pediatrics, Allergy and Immunology