Lack of CD40-dependent B-cell proliferation in B lymphocytes isolated from patients with persistent polyclonal B-cell lymphocytosis.
Persistent B-cell lymphocytosis (PPBL) is a haematological disorder diagnosed primarily in adult female smokers that is characterized by a polyclonal increase in peripheral blood B lymphocytes and a moderate elevation of serum IgM. B lymphocyte-associated cellular abnormalities, such as the occurrence of multi-lobed nuclei, increased bcl2/Ig gene rearrangements and the identification of an extra long-arm chromosome (i3)(q10) in the B-cell population, indicate that PPBL could be part of a multi-step process leading to the emergence of a malignant B lymphoproliferation. However, the resulting impact on cellular functional properties remains to be elucidated. Our goal was to address that aspect via the study of B-cell activity following stimulation through CD40, a key molecule of the tumour necrosis factor receptor superfamily involved in B lymphocyte development. In contrast to normal B cells, PPBL B lymphocytes were unable to respond to the proliferative signal delivered in vitro by CD40, indicating a defect in the CD40 activation pathway. Polymerase chain reaction amplification and sequencing of the receptor as well as FACScan analysis of patient B lymphocytes dismissed the possibility of a defect in either CD40 structure or expression. Moreover, Western blot analysis of tyrosine phosphorylation, an early event in the CD40-signalling cascade, was similar in patients and controls, leading to the conclusion that the defect affecting B lymphocytes in PPBL patients is probably located downstream of that signalling cascade.
Loembé
M M
MM
CREFSIP, Départment de Biochimie and Microbiologie, Université Laval, and Centre d'hématologie et d'immunologie clinique, CHA, Québec, Canada.
Lamoureux
J
J
Deslauriers
N
N
Darveau
A
A
Delage
R
R
D000328:Adult; D001402:B-Lymphocytes / Q000166:cytology* / Q000276:immunology; D015153:Blotting, Western; D019013:CD40 Antigens / Q000032:analysis / Q000276:immunology*; D002455:Cell Division / Q000276:immunology; D002478:Cells, Cultured; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008218:Lymphocytosis / Q000276:immunology*; D008875:Middle Aged; D010766:Phosphorylation; D016133:Polymerase Chain Reaction; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics; D015398:Signal Transduction
D019013:CD40 Antigens; D018124:Receptors, Tumor Necrosis Factor