The article published by Chlewicki et al. in the June 15, 2008 issue of The JI (1) presents a series of experiments demonstrating the complexity of activating vs inhibitory signals that can be imparted by the 2B4 (CD244)-CD48 interaction. However, direct correlation of these findings in vivo is still unclear. The authors noted that one possible demonstration of the in vivo inhibitory function of CD244 is demonstrated by EBV infection in that CD48 is up-regulated on EBV-infected B cells and may therefore account for the failure of infected cells to be lysed by activated NK cells. However, there may be additional factors involved that contribute to the insensitivity. In this regard, we wish to remind the authors of a finding published in The JI in 2006 (2) showing that nontransformed mouse B cells can stimulate cytokine secretion by IL-2-propagated NK cells and that this interaction is mediated by the interaction between CD244 on NK cells and CD48 on B cells. It is interesting that in contrast to the hypothesis posed by the authors, this interaction occurring in mouse does not result in lysis of B cells.

Chlewicki, L. K., C. A. Velikovsky, V. Balakrishnan, R. A. Mariuzza, V. Kumar.
. Molecular basis of the dual functions of 2B4 (CD244).
J. Immunol.
Gao, N., P. Schwartzberg, J. A. Wilder, B. R. Blazar, D. Yuan.
. B cell induction of IL-13 expression in NK cells: role of CD244 and SLAM-associated protein.
J. Immunol.