Table 1. The basis of defects in Severe Combined Immunodeficiency.

Mutations in IL2RG or JAK3 genes cause defects in T and NK cell development, with functional abnormalities of B cell lineage in human and lack of B cells in mice. IL7R mutations greatly diminish T cell numbers, with normal or even increased number of B and NK cells. IL2RB mutations result in defective NK cell development but do not affect T and B cell development.

Form of SCID	Lineage abnormalities	Causes of defects	References
X-linked SCID	TB+NK−. T and NK cells absent; B cells present but non-functional.	The disease results from mutations in the IL2RG gene. Decreased T cell development is due to defective IL-7- induced signaling. Lack of NK cell development is the result of defective IL-15-induced signaling. Functional B cell abnormalities are due to a lack of T-cell help and defects in IL-4 and IL- 21-induced signaling, as indicated by the pan-hypogammaglobulinemia found in Il4/Il21r double KO mice, which is associated with germinal center abnormalities in these mice57	1,5
JAK3- deficient SCID	TB+NK−. T and NK cells absent; B cells present but non-functional.	The disease results from mutations in the JAK3 gene. Abnormalities are due to same reasons as in XSCID.	11,12
IL7R- deficient SCID	TB+NK+−. T cells absent. In humans B cells are present but in Il7r- deficient mice, B cells are absent.	Defective IL-7-induced signaling with a possible partial contribution from TSLP. Humans with IL7-deficiency have not been reported. Mice with Il7r deficiency have a somewhat more severe T cell phenotype than mice with Il7 deficiency.	13,42,43
IL2RB- deficient SCID	T+B+NK−. NK cells absent.	Defective IL-15-induced signaling, based on Il15, Il15ra, and Il2rb deficient mice, IL2RB-deficient SCID, and in vitro studies.	1,146