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

Abstract

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.