Regulation of CD23 isoforms on B-chronic lymphocytic leukemia.
CD23 is constitutively and atypically expressed on malignant B-cells in patients with chronic lymphocytic leukemia. It exists in two isoforms that differ only in a short amino acid sequence at the N-terminus. The CD23a isoform exhibits an endocytosis signal, that renders it more efficient in antigen uptake than CD23b. Therefore, we analyzed the regulation of CD23 isoforms and tested the ability to stimulate T-cell clones by targeting antigen to CD23 on CLL B-cells. Investigation of several stimulators to promote CD23a expression on CLL versus normal B-cells confirmed a different CD23 regulation in B-CLL. We did not find any evidence for a differential regulation of the two CD23 isoforms in B-CLL. However, CD23a is always predominantly expressed with a constant ratio of CD23a:CD23b. We show that antigen targeted to CD23 on CLL B-cells is very efficiently presented. Therefore, CD23 is likely to provide a suitable target for receptor-mediated antigen presentation in B-CLL which can be used to activate a T-cell response.
Goller
Martin E
ME
Department of Rheumatology and Immunology, Medizinische Poliklinik, University of Würzburg, Klinikstrasse 6-8, Würzburg, Germany.
Kneitz
Christian
C
Mehringer
Claudia
C
Müller
Karin
K
Jelley-Gibbs
Dawn M
DM
Gosselin
Edmund J
EJ
Wilhelm
Martin
M
Tony
Hans Peter
HP
D017951:Antigen Presentation; D000941:Antigens / Q000378:metabolism; D001402:B-Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D004705:Endocytosis; D015973:Gene Expression Regulation, Leukemic / Q000187:drug effects; D006801:Humans; D007167:Immunotherapy; D015847:Interleukin-4 / Q000494:pharmacology; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics* / Q000473:pathology; D008213:Lymphocyte Activation; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000378:metabolism*; D020033:Protein Isoforms / Q000096:biosynthesis* / Q000235:genetics; D017455:Receptors, IgE / Q000096:biosynthesis* / Q000235:genetics; D013601:T-Lymphocytes / Q000276:immunology; D014407:Tumor Cells, Cultured / Q000276:immunology
D000941:Antigens; D009363:Neoplasm Proteins; D020033:Protein Isoforms; D017455:Receptors, IgE; D015847:Interleukin-4