Direct cellular interaction with activated CD4+ T cells overcomes hyporesponsiveness of B-cell chronic lymphocytic leukemia in vitro

Theresa Tretter, Martin Schuler, Folker Schneller, Ute Brass, Marion Esswein, M. Javad Aman, Christoph Huber, Christian Peschel

Research output: Contribution to journalArticlepeer-review

30 Scopus citations

Abstract

The proliferative response of clonal B cells from patients with chronic lymphocytic leukemia (B-CLL) is drastically reduced compared to normal B lymphocytes stimulated via the B cell antigen receptor complex or by CD40 ligation. In the present study we demonstrate that hyporesponsiveness of CLL- B cells can be overcome by stimulatory pathways mediated by activated CD4+ T cells. In contrast to CD40 ligation, costimulation with activated T cells promotes a proliferative response in CLL-B cells identical to that in normal B cells. Furthermore, coculture with activated T cells improved survival of CLL-B cells in vitro. Differentiation of CLL-B cells into IgM producing cells was promoted, as well. However, the capacity for IgM secretion remained impaired compared to that of normal B cells. For T-cell-mediated B cell activation direct cellular contact with activated T helper cells is absolutely required. Prevention of CD40/CD40L interaction by CD40 antibody caused only partial inhibition of B cell activation, suggesting that additional signals are involved in T-B cell interaction. Whereas interruption of the ligand pairs CD11a/CD54, CD5/CD72, CD27/CD70 had no influence, the addition of CD58 antibody completely inhibited B cell activation by activated T cells. In costimulation with cellular signals the presence of B-cell- tropic cytokines, such as IL-2 and IL-4, was required to optimize B-CLL proliferation, as demonstrated by the use of neutralizing antibodies. We conclude from these results that proliferative hyporesponsiveness by CLL-B cells can be circumvented by antigen-nonspecific signals in addition to CD40 which are mediated by direct contact with activated T helper cells.

Original languageEnglish
Pages (from-to)41-50
Number of pages10
JournalCellular Immunology
Volume189
Issue number1
DOIs
StatePublished - 10 Oct 1998

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