A human non-XLA immunodeficiency disease characterized by blockage of B cell development at an early proB cell stage.
We report a detailed analysis of a B cell defect affecting a patient girl born from first cousin parents, characterized by a severe non-X-linked agammaglobulinemia with a total absence of CD19- cells in the periphery. In the bone marrow, CD19 expression was also highly impaired, resulting in the absence of both B and preB compartments. By contrast, CD34+CD10+, CD34psiL+, and some CD19+CD10+ mostly CD34+ early proB cells were present, although diminished. Semiquantitative RT-PCR analysis performed on mononuclear bone marrow cells indicated that lambda-like, VpreB, Rag-1, Rag-2, and TdT transcripts expressed during proB cell stages were found at normal levels whereas E2A, CD10, Syk, Pax-5, CD19, Igalpha, Igbeta, VH-Cmu, and Vkappa-Ckappa transcripts characteristic of later stages were severely depressed. This phenotype resembles that of Pax-5 knock-out mice, but since the coding sequence of the patient Pax-5 cDNA was shown to be normal, the defect might rather result from an altered regulation of this gene. All these data indicate that the patient suffers from a new genetic defect that results in an arrest of differentiation within the proB cell compartment, i.e., earlier than X-linked agammaglobulinemia, before the onset of Ig gene rearrangements.
Meffre
E
E
Centre d'Immunologie de Marseille-Luminy, Marseille, France.
LeDeist
F
F
de Saint-Basile
G
G
Deville
A
A
Fougereau
M
M
Fischer
A
A
Schiff
C
C
D000361:Agammaglobulinemia / Q000235:genetics* / Q000276:immunology*; D018941:Antigens, CD19 / Q000032:analysis; D001402:B-Lymphocytes / Q000276:immunology* / Q000473:pathology; D001853:Bone Marrow / Q000276:immunology; D001854:Bone Marrow Cells; D002454:Cell Differentiation; D003001:Cloning, Molecular; D004268:DNA-Binding Proteins / Q000032:analysis / Q000235:genetics; D004303:Dosage Compensation, Genetic; D005260:Female; D018507:Gene Expression Regulation, Developmental; D030342:Genetic Diseases, Inborn / Q000276:immunology* / Q000473:pathology; D006412:Hematopoietic Stem Cells / Q000276:immunology*; D006650:Histocompatibility Testing; D006801:Humans; D007223:Infant; D018448:Models, Immunological; D009687:Nuclear Proteins / Q000032:analysis / Q000235:genetics; D051757:PAX5 Transcription Factor; D016133:Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D014157:Transcription Factors
D018941:Antigens, CD19; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D051757:PAX5 Transcription Factor; C497281:PAX5 protein, human; D014157:Transcription Factors