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

作者：MILILI M; LEDEIST F; DESAINTBASILE G; FISCHER A; FOUGEREAU M; SCHIFF C

来源：Journal of Clinical Investigation, 1993, 91(4): 1616-1629.

DOI：10.1172/JCI116369

• IMMUNOGLOBULIN
• IMMUNOGLOBULIN-RELATED GENE EXPRESSION
• PRIMARY IMMUNE DEFICIENCY

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.

• 出版日期1993-4