Bone marrow cells in X-linked agammaglobulinemia express pre-B-specific genes (lambda-like and V pre-B) and present immunoglobulin V-D-J gene usage strongly biased to a fetal-like repertoire.
Expression of Ig and Ig-related genes has been studied in bone marrow cells from two patients with severe form of X-linked agammaglobulinemia (XLA). Phenotypic analysis revealed the presence of pre-B cells, in the absence of mature B cell markers. The pre-B-specific genes, lambda-like and V pre-B, were normally transcribed. Sequence analysis of 48 distinct V-D-J cDNA clones directly derived from XLA bone marrow cells indicated that they had characteristics of an early fetal pre-B repertoire. All VH families were identified, with a strong bias in the gene usage: a few VH genes were largely overexpressed, either germline or slightly mutated; most genes had been located 3' of the VH locus and were also used in fetal liver (8-13 wk of gestation). Short D regions, (resulting from D-D fusion, making usage of all D genes in both orientations with utilization of the three reading frames), restricted N diversity, and a fetal JH usage pattern were also observed. Taken together, our data suggest that the XLA defect does not alter V-D-J rearrangements nor the expression of mu, lambda-like, and V pre-B transcripts and most likely results in a poor efficiency of some critical steps of the B cell maturation.
Milili
M
M
Centre d'Immunologie Institut National de la Santé et de la Recherche Médicale (INSERM) Centre National de la Recherche, Scientifique (CNRS), Marseille-Luminy, France.
Le Deist
F
F
de Saint-Basile
G
G
Fischer
A
A
Fougereau
M
M
Schiff
C
C
D000328:Adult; D000361:Agammaglobulinemia / Q000235:genetics*; D001402:B-Lymphocytes / Q000166:cytology*; D001483:Base Sequence; D001853:Bone Marrow / Q000503:physiopathology; D001854:Bone Marrow Cells; D002675:Child, Preschool; D005333:Fetus / Q000502:physiology; D015328:Gene Rearrangement, B-Lymphocyte, Light Chain; D005803:Genes, Immunoglobulin / Q000235:genetics; D005802:Genes, MHC Class II / Q000235:genetics; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D010641:Phenotype; D016364:Reading Frames; D011995:Recombination, Genetic; D013234:Stem Cells / Q000276:immunology; D014960:X Chromosome