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B-cell chronic lymphocytic leukemia (B-CLL) is characterized by a sustained accumulation of long-lived and well-differentiated B lymphocytes in lymphoid tissues, peripheral blood and bone marrow. Although the pathogenesis of this disease is not entirely understood, altered apoptosis is believed to play a relevant role in B-CLL. In this study, we compared the expression of CD95, the best characterized surface molecule involved in triggering the apoptotic machinery, on normal and CLL B cells before and after in vitro activation with polyclonal stimulators. Cell activation was monitored by verifying the induced expression of the early activation antigen CD69. Freshly analyzed CLL B cells showed significantly lower levels of CD95 than normal B cells. Moreover, following in vitro culture with phorbol 12-myristate 13-acetate (PMA) + ionomycin, phytohemagglutinin, or pokeweed mitogen, CLL B cells failed to upregulate CD95 expression as efficiently as normal B cells. Impairment of CD95 upregulation was mainly observed following PMA + ionomycin treatment. In contrast, CLL B cells were shown to express CD69 as well as normal B cells, regardless of the activator used, indicating that CLL B cells retain the ability to respond to activating stimuli but are unable to efficiently implement the CD95-mediated activation-induced cell death (AICD) program. In conclusion, these results suggest that prolonged survival of CLL B cells may be contributed to by alterations in AICD mechanisms.

Newborns are more susceptible than adults to infections, which suggests a relative immaturity of the immune system early after birth. Cord blood T cells differ significantly both in surface phenotype and function from adult T cells. We examined the proliferation and expression of activation molecules by lymphocytes isolated from umbilical cord blood or peripheral blood of adults. The lymphocytes were cultured for 5 days in the presence of phytohemagglutinin, concanavalin A, or anti-CD3 monoclonal antibody. Cord blood T cells expressed the CD45RA molecule, while a low proportion expressed the RO isoform, a marker of primed or activated lymphocytes. Furthermore, more than 95% of neonatal lymphocytes bear the CD38 molecule, but do not express the CD57 molecule. After stimulation by phytohemagglutinin or concanavalin A, the lymphocytes from newborns were activated and proliferated as efficiently as adult T cells. Anti-CD3 did not cause neonatal lymphocytes to proliferate, but these cells expressed activation molecules, such as HLA-DR antigens and the receptor for interleukin-2 and transferrin. The relevance of these findings to tolerance induction in immature cord blood T cells is discussed.