Inhibition of T cell/B cell interaction by B-CLL cells.
The course of disease in patients suffering from chronic lymphocytic leukemia (CLL) is determined by a profound dysregulation of the immune system. The resulting immune suppression is the main cause of death in those patients. In the present study we addressed the question of whether leukemic B cells (B-CLL) are able to suppress regular T cell/B cell interaction. Activated CD4+ T cell clones induce expression of the early activation antigen CD23 on B lymphocytes in vitro. Under conditions used, this B cell activation event was dependent upon direct T cell contact. Addition of certain bystander B-CLL cells or normal B lymphocytes resulted in a cell number-dependent inhibition of B cell induction. This seems to reflect the competition of B-CLL cells for a cell contact-mediated T cell helper signal. By using CD40 ligand transfected fibroblasts as a substitute for T cell help, we show that the same B-CLL cells also suppress CD40 ligand-mediated B cell activation. B-CLL cells differ in their ability to inhibit CD40 ligand-mediated B cell activation. Some B-CLL cases (eight out of 14) are unable to compete for the T cell or CD40 ligand-mediated signal, even though they can functionally interact with CD40 ligand and thereby get activated themselves. In addition, these results indicate that the observed inhibition is not a result of cell crowding by merely reducing the chance of specific B cell/T cell interactions. Collectively, these data indicate that B-CLL cells are able to inhibit the interaction of activated T lymphocytes with normal B lymphocytes in vitro. Perturbed T cell/B cell interaction may represent an important mechanism underlying the various defects of the specific immune system observed in patients suffering from B-CLL.
Medizinische Poliklinik der Universität Würzburg, Germany.
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C
Kneitz
M
M
Goller
M
M
Wilhelm
C
C
Mehringer
G
G
Wohlleben
A
A
Schimpl
H P
HP
Tony
D015703:Antigens, CD / Q000097:blood; D001402:B-Lymphocytes / Q000276:immunology*; D019013:CD40 Antigens / Q000276:immunology; D023201:CD40 Ligand; D002450:Cell Communication; D002478:Cells, Cultured; D002999:Clone Cells; D005434:Flow Cytometry; D006681:HLA-D Antigens / Q000097:blood; D006801:Humans; D016130:Immunophenotyping; D007700:Kinetics; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000097:blood / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000235:genetics; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D014162:Transfection
D015703:Antigens, CD; D019013:CD40 Antigens; D006681:HLA-D Antigens; D008562:Membrane Glycoproteins; D023201:CD40 Ligand