Aberrant expression and reverse signalling of CD70 on malignant B cells

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Abstract
In normal lymphoid tissues the tumour necrosis factor‐receptor family member CD27 and its ligand CD70 have a restricted expression pattern. Previously, we reported that expression of CD27 is deregulated in B‐cell leukaemias and lymphomas. Here we show that, although infrequently expressed by normal human B cells in vivo, CD70 is found on 50% of B‐CLLs, 33% of follicle centre lymphomas, 71% of large B‐cell lymphomas, and 25% of mantle cell lymphomas. Interestingly, in the majority of leukaemias and lymphomas examined, CD70 was found to have a capped appearance, a feature that coincided with co‐expression of CD27. Functional analysis showed that a subset of B‐CLLs could proliferate vigorously in response to CD70 mAb but not to CD27 mAb. This response was synergistically enhanced by ligation of CD40 but inhibited by the presence of IL‐4. Additional experiments indicated that the proliferative response was due to an agonistic signal delivered via CD70, rather than blocking of negative signalling by CD27. Thus, next to its role as ligand, in a subset of malignant B cells CD70 can operate as receptor and as such might contribute to progression of these B‐cell malignancies.