Staphylococcus aureus Cowan strain 1 activation of B-chronic lymphocytic leukaemia cells augments the response to CD40 stimulation.
The signals involved in regulating the proliferation, differentiation and survival of B-chronic lymphocytic leukemia (B-CLL) cells are fully understood. B-CLL cells have been found to respond poorly to various activation signals and only after successful Epstein-Barr virus (EBV) transformation has it been possible to maintain such cells in long-term cultures. In this work we describe a new method to activate and induce proliferation in B-CLL cells and to maintain such cells in long-term culture for longer than 1 month. We used a combination of protocols in an attempt to mimic some of the signals of a thymus-dependent immune response. The B-CLL cells were first activated with Staphylococcus aureus Cowan strain 1 (SAC) particles plus thioredoxin (Trx), followed by stimulation with interleukin (IL)-2 + Trx. This treatment primed the cells for further stimulation with anti-CD40 monoclonal antibody (MoAb) presented on irradiated CD32L cells (the CD40-system) or soluble CD40 Ligand, and a combination of Trx and cytokines (IL-4 + IL-10), which allowed the cells to be maintained for up to 1 month with preserved viability and a variable rate of proliferation. However, induced proliferation of the B-CLL cells was limited to approximately 1 month, suggesting that additional signals are required to facilitate further proliferation.
Söderberg
O
O
Instituto de Patologia e Imunologia Molecular da Universidade do Porto (IPATIMUP), Porto, Portugal.
Thunberg
U
U
Weigelt
C
C
Christiansen
I
I
Tötterman
T H
TH
Carlsson
M
M
Sällström
J
J
Nilsson
K
K
D002051:Burkitt Lymphoma / Q000276:immunology*; D019013:CD40 Antigens / Q000276:immunology*; D018929:Cell Culture Techniques / Q000379:methods*; D002453:Cell Cycle; D005260:Female; D006412:Hematopoietic Stem Cells; D004854:Herpesvirus 4, Human / Q000302:isolation & purification; D006801:Humans; D008213:Lymphocyte Activation; D008297:Male; D010641:Phenotype; D011947:Receptors, Antigen, B-Cell / Q000276:immunology*; D013211:Staphylococcus aureus / Q000276:immunology*; D014407:Tumor Cells, Cultured
D019013:CD40 Antigens; D011947:Receptors, Antigen, B-Cell