Lysophosphatidic acid (LPA) promotes survival, growth, differentiation, and motility in a variety of cell types, and has been reported to act as a cell survival and growth factor in B lymphocytes. Autotaxin (ATX), through its lysophospholipase D activity, generates LPA from lysophosphatidylcholine (LPC). In this study, we investigated the effects of LPA and also the expression of ATX and LPA receptor, in the human pre-B-cell line Nalm-6. It was found that LPA protects Nalm-6 cells against both spontaneous and staurosporine-induced apoptosis. Furthermore, ATX expression on the cell surface and ATX activity in the cell lysate were detected. No accumulation of LPA in the culture medium was, however, detected when the Nalm-6 cells were cultured with LPC. The pre-B cells were found to express the mRNA transcript for lipid phosphate phosphatase-1 and LPA degradation was inhibited in the presence of the phosphatase inhibitor vanadate, it was surmised that LPA production in the culture medium may have been masked by LPA degradation by this ecto-phosphatase. Abundant expression of LPA receptors, especially, LPA(4), was detected by a real-time polymerase chain reaction technique. Our results suggest an important and autocrine role of LPA in the survival of this well-established model cell line, although the direct involvement of ATX in the production of LPA in these cells was not confirmed.