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J. Exp. Med.,
Volume 187, Number 4, February 16, 1998 609-618
By
From the Department of Molecular and Cell Biology and the Cancer Research Laboratory, University
of California at Berkeley, Berkeley, California 94720
The formation of the repertoire of mouse natural killer (NK) cell receptors for major histocompatibility complex (MHC) class I molecules was investigated by determining the developmental pattern of Ly49 receptor expression. During the first days after birth, few or no splenic
NK cells express Ly49A, Ly49C, Ly49G2, or Ly49I receptors. The proportion of Ly49+
splenic NK cells gradually rises to adult levels during the first 6-8 wk of life. The appearance of
appreciable numbers of splenic Ly49+ NK cells coincides with the appearance of NK activity at
3-4 wk. After in vivo transfer, NK cells not expressing specific Ly49 receptors can give rise to
NK cells that do, and cells expressing one of these four Ly49 receptors can give rise to cells expressing others. Once initiated, expression of a Ly49 receptor is stable for at least 10 d after in
vivo transfer. Hence, initiation of Ly49 receptor expression occurs successively. Interestingly,
expression of one of the receptors tested, Ly49A, did not occur after in vivo transfer of Ly49A
cells. One possible explanation for these data is that the order of Ly49 receptor expression by
NK cells is nonrandom. The results provide a framework for evaluating models of NK cell repertoire formation, and how the repertoire is molded by host class I MHC molecules.
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