Human severe combined immunodeficiency disease: phenotypic and functional characteristics of peripheral B lymphocytes.
Human severe combined immunodeficiency disease (SCID) includes an X-chromosome-linked type characterized by a complete absence of mature T cells, hypogammaglobulinemia but normal or elevated number of B cells, suggesting that the disease results from a block in early T cell differentiation. It has been shown that B cells from obligate carrier women of this disorder exhibit the preferential use of the nonmutant X chromosome as the active X (as shown for T cells), suggesting that the SCID gene product has a direct effect on B cells as well as on T cells. To examine this question, we analyzed the phenotypic and functional characteristics of peripheral B cells from nine infants with SCID. We found a constant absence of spontaneously expressed activation Ag on B cell membrane from all SCID patients tested which contrasts with the phenotypic pattern exhibited by age-matched infants whom all cells bearing surface Ig express the 4F2 Ag and to a lesser extent the transferrin receptor. Concurrently, B cells from SCID patients have a profound impairment in their responses to stimuli that induce in vitro B cell proliferation and differentiation. Although rIL-2 and low-Mr B cell growth factor are potent inducers of proliferation on age-matched infants' B cells, they are poorly efficient in inducing proliferation of anti-mu-activated SCID B cells. This impairment is not related to the resting B cell phenotype of SCID B cells as shown by comparison with normal resting B cells. Furthermore, we observed an apparent block in B cell differentiation inasmuch as neither rIL-2 nor rIL-6 could support SAC-activated SCID B cell differentiation, both lymphokines being very efficient in inducing SAC-activated age-matched infants' B cell or purified resting B cell differentiation. These results suggest that the SCID gene defect has a direct effect on B cells and is required during B cell maturation.
Unité d'Immunologie, INSERM U 132, Paris, France.
M L
ML
Gougeon
G
G
Drean
F
F
Le Deist
M
M
Dousseau
M
M
Fevrier
A
A
Diu
J
J
Theze
C
C
Griscelli
A
A
Fischer
D015703:Antigens, CD / Q000032:analysis*; D000954:Antigens, Surface / Q000032:analysis; D001402:B-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation; D005434:Flow Cytometry; D006684:HLA-DR Antigens / Q000032:analysis*; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000276:immunology*; D007223:Infant; D007231:Infant, Newborn; D007376:Interleukin-2 / Q000494:pharmacology; D015850:Interleukin-6 / Q000494:pharmacology; D008213:Lymphocyte Activation; D011947:Receptors, Antigen, B-Cell / Q000032:analysis*; D011990:Receptors, Transferrin / Q000378:metabolism
D015703:Antigens, CD; D000954:Antigens, Surface; D006684:HLA-DR Antigens; D007376:Interleukin-2; D015850:Interleukin-6; D011947:Receptors, Antigen, B-Cell; D011990:Receptors, Transferrin