Absence of major histocompatibility class II expression does not impair hematopoiesis in mice.
OBJECTIVE
Major histocompatibility class II (MHC II) molecules are among the earliest antigens to be expressed in hematopoietic progenitor cells; however, the functional role of these molecules in hematopoiesis remains controversial. We examined the role of MHC II antigens during hematopoiesis using a mouse model of MHC II deficiency related to the absence of the critical transcriptional activator, CIITA.


METHODS
Sca-1(-), Sca-1(+)lin(+), and Sca-1(+)lin(-) populations of marrow cells from CIITA(-)(/-) and wild-type mice were analyzed by immunofluorescence for MHC II expression. Hematopoietic capacity was assessed in CIITA(-/-) and wild-type mice by CFU-S, CFU-GM, and radiation sensitivity assays.


RESULTS
Flow cytometric characteristics of hematopoietic progenitors from CIITA(-/-) and wild-type mice were identical except for the absence of MHC II expression in CIITA null mice. There were no significant differences in capacity for hematopoietic reconstitution and clonogenicity as measured by radiation sensitivity, CFU-S, and CFU-GM assays among CIITA(-/-) and wild-type mice.


CONCLUSIONS
These experiments show that downregulation of MHC II gene transcription does not effectively alter normal hematopoiesis, and provide strong evidence that MHC II expression on hematopoietic progenitors is not required for normal hematopoietic development.
Benito
A I
AI
Program in Human Immunogenetics, Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109-1024, USA.
Milner
L A
LA
Leisenring
W
W
Deeg
H J
HJ
Woolfrey
A E
AE
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D003114:Colony-Forming Units Assay; D004195:Disease Models, Animal; D005434:Flow Cytometry; D006410:Hematopoiesis / Q000187:drug effects* / Q000528:radiation effects; D006412:Hematopoietic Stem Cells / Q000166:cytology; D000949:Histocompatibility Antigens Class II / Q000494:pharmacology* / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D009687:Nuclear Proteins; D012376:Rodent Diseases / Q000235:genetics / Q000276:immunology*; D016511:Severe Combined Immunodeficiency / Q000235:genetics / Q000276:immunology / Q000662:veterinary*; D015534:Trans-Activators / Q000235:genetics / Q000494:pharmacology; D014916:Whole-Body Irradiation / Q000401:mortality
D000949:Histocompatibility Antigens Class II; C083728:MHC class II transactivator protein; D009687:Nuclear Proteins; D015534:Trans-Activators