title: Agammaglobulinemia associated with BCR⁻ B cells and enhanced expression of CD19.
abstract: Expression of a BCR is critical for B-cell development and survival. We have identified 4 patients with agammaglobulinemia and markedly reduced but detectable B cells in the peripheral circulation. These B cells have an unusual phenotype characterized by increased expression of CD19 but no BCR. The cells are positive for CD20, CD22, and CD38, but not for Annexin 5 or activation markers, including CD69, CD83, or CD86. EBV lines derived from these B cells lack functionally rearranged immunoglobulin heavy-chain transcripts, as shown by PCR-rapid amplification of cDNA ends (PCR-RACE). Analysis of BM from 2 of the patients showed a severe reduction in the number of pro-B cells as well as pre-B cells. Functionally rearranged heavy-chain transcripts were identified, indicating that machinery to rearrange immunoglobulin genes was intact. Flow cytometry of B-lineage cells suggested accelerated acquisition of maturation markers in early B-cell precursors and increased phosphorylation of signal transduction molecules. Further, expression of TdT, a molecule that is normally down-regulated by a functional pre-BCR complex, was decreased. We hypothesize that the accelerated maturation, increased expression of CD19, and lack of a BCR were due to the constitutive activation of the BCR signal transduction pathway in these patients.
authors.affiliation: Department of Immunology, St Jude Children's Research Hospital, Memphis, TN 38105, USA
authors.forename: A Kerry
authors.initials: AK
authors.lastname: Dobbs
authors.forename: Amma
authors.initials: A
authors.lastname: Bosompem
authors.forename: Elaine
authors.initials: E
authors.lastname: Coustan-Smith
authors.forename: Gayle
authors.initials: G
authors.lastname: Tyerman
authors.forename: Frank T
authors.initials: FT
authors.lastname: Saulsbury
authors.forename: Mary Ellen
authors.initials: ME
authors.lastname: Conley
mesh_terms: D000293:Adolescent; D000328:Adult; D000361:Agammaglobulinemia / Q000276:immunology*; D018941:Antigens, CD19 / Q000235:genetics / Q000276:immunology*; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D005260:Female; D017353:Gene Deletion; D005786:Gene Expression Regulation; D006801:Humans; D007223:Infant; D038041:Lymphopoiesis; D008297:Male; D054448:Precursor Cells, B-Lymphoid / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D051562:Proto-Oncogene Proteins c-bcr / Q000235:genetics / Q000276:immunology*; D055815:Young Adult
chemical_list: D018941:Antigens, CD19; C496613:BCR protein, human; D051562:Proto-Oncogene Proteins c-bcr