Evidence for failure of V(D)J recombination in bone marrow pre-B cells from X-linked agammaglobulinemia.

Schwaber, Jerrold

doi:10.1172/jci115817

Cited by 6 publications

(2 citation statements)

References 30 publications

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“…These results are in agreement with previous phenotypic characterization ofthe bone marrow cell population in XLA patients (62,63). By contrast to other reports (3,9,49,64), our data indicate that rearrangement mechanisms seem fully functional, although a possible decrease in efficiency ofthe pro-B to pre-B transition, as followed by the DJ to VDJ rearrangement cannot be quantitatively as- Our analysis performed on XLA bone marrow cells provides direct access to the pre-B cell repertoire which is truly representative of the defect. Analysis of EBV clones derived from XLA patients may therefore contain a bias linked to the selection ofa minor population of B cells that have escaped the XLA defect (1 1, 12).…”

Section: Methodscontrasting

confidence: 97%

“…region revealed that most transcripts encompassed the V region (at least 66%), whereas 1 1% were clearly of the D-J-CM type. This already indicates that transcription is not limited to Du (9) or of the more recently described LS-Cg transcripts (49). This finding prompted analysis of complete VDJ (COt) transcripts that were easily derived upon amplification with primers specific ofthe various VH-leader sequences and ofthe CQ 5' region.…”

Section: Methodsmentioning

confidence: 95%

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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.

Milili

Deist²,

Basile³

et al. 1993

J. Clin. Invest.

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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, X-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 u, X-like, and V pre-B transcripts and most likely results in a poor efficiency of some critical steps of the B cell maturation. (J. Clin. Invest. 1993.91:1616-1629

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Section: Methodscontrasting

confidence: 97%

Section: Methodsmentioning

confidence: 95%

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.

Milili

Deist²,

Basile³

et al. 1993

J. Clin. Invest.

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Predominance of sterile immunoglobulin transcripts in a female phenotypically resembling Bruton's agammaglobulinemia

et al. 1995

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The transcription pattern of the heavy chain immunoglobulin gene locus was analyzed in a 6-month-old female with agammaglobulinemia characterized by the absence of mature B cells in peripheral blood, arrested B cell development in the bone marrow and lack of germinal center development. DNA sequencing provided no evidence of mutations within the coding region of the Bruton's tyrosine kinase gene. Polymerase chain reaction-generated cDNA libraries from blood and bone marrow were screened initially using JH and CH oligodeoxynucleotide probes and VH family-specific probes. Only 10% of the transcripts constituted mature VDJC mu recombinations. Ninety percent of the cDNA were sterile immunoglobulin transcripts comprised of: DJC mu (DH-JHC mu), JC mu (JH-C mu), EC mu (enhancer spliced to C mu), SC mu and IC mu [corresponding to switch (S) and intron (I) regions spliced to C mu]. In the mature immunoglobulin transcripts, VH use indicated germline expression with little evidence of somatic mutation. All cDNA were of the C mu type. Different D segments, D-D joining events and unknown D-like elements were noted in the DJC mu and VDJC mu transcripts. This pattern of immunoglobulin rearrangements, along with the phenotypic cell surface antigen characteristics (CD19-), suggest that an earlier arrest in B cell development than is characteristic of Bruton's X-linked agammaglobulinemia has occurred in this patient.

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Antibody Deficiencies Reflect Abnormal B Cell Diffrentiation

Cooper

Nishimoto

Lassoued

et al. 1993

Progress in Immunology Vol. VIII

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Evidence for failure of V(D)J recombination in bone marrow pre-B cells from X-linked agammaglobulinemia.

Cited by 6 publications

References 30 publications

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.

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.

Predominance of sterile immunoglobulin transcripts in a female phenotypically resembling Bruton's agammaglobulinemia

Antibody Deficiencies Reflect Abnormal B Cell Diffrentiation

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