title: Impaired responsiveness to B cell growth factor in a patient with common variable hypogammaglobulinemia.
abstract: Common variable hypogammaglobulinemia (CVH) is a clinical syndrome that includes a diverse group of patients with heterogeneous defects resulting in impaired B cell proliferation and terminal differentiation into mature plasma cells capable of normal immunoglobulin synthesis and secretion. In this study, we report our identification of a previously undescribed intrinsic B cell defect in a patient with CVH. This patient's B cells showed a marked impairment in hemolytic plaque-forming cell (HePFC) formation compared with control B cells (15 v 80 HePFCs per culture, respectively). In addition, this patient's B cells displayed decreased B cell colony formation compared with control B cells (5 +/- 2 v 93 +/- 8, respectively). When examined for their responsiveness to phytohemagglutinin-T cell conditioned media (PHA-TCM), the patient's B cells displayed impaired B cell proliferation compared with control B cells (stimulation index [SI] 1.3 +/- 0.20 v 26 +/- 1.4 with 20% control PHA-TCM [vol/vol]). Impaired proliferation by the patient's B cells persisted with increasing concentrations of B cell growth factor (BCGF). Additionally, PHA-TCM prepared from the patient's T cells when compared with control PHA-TCM consistently showed less support for control B cell proliferation (SI 1.27 +/- 0.21 v 26 +/- 1.4, respectively). In coculture studies of B cell proliferation and immunoglobulin synthesis, patient's T cells showed no evidence of an enhanced suppressive effect or decreased helper effect. This patient's immune defects involve, first, an intrinsic B cell defect characterized by an impaired responsiveness to BCGF's proliferation signal and, second, impaired production of BCGF by the patient's T cells.
authors.forename: R T
authors.initials: RT
authors.lastname: Perri
authors.forename: D J
authors.initials: DJ
authors.lastname: Weisdorf
mesh_terms: D000328:Adult; D000361:Agammaglobulinemia / Q000276:immunology*; D001402:B-Lymphocytes / Q000145:classification / Q000276:immunology* / Q000473:pathology; D002455:Cell Division; D002478:Cells, Cultured; D003470:Culture Media; D005260:Female; D006133:Growth Substances / Q000276:immunology*; D006462:Hemolytic Plaque Technique; D006801:Humans; D015847:Interleukin-4; D008222:Lymphokines / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
chemical_list: D003470:Culture Media; D006133:Growth Substances; D008222:Lymphokines; D015847:Interleukin-4