Genetics, Regulation, and Specificity of Murine Natural Antitumor Antibodies and Natural Killer Cells23

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Abstract
A concurrent study of specificity, regulation, ontogeny, and genetics of murine natural killer (NK) cell and natural antibody (NAb) activities [in DBA/2, CBA/J, A/Sn, and A/J inbred mice, Bg/Bg and Bg/+ mice of the inbred C57BLl6J background, (C57BL/6 × DBA/2}F1 mice, and (CBA × DBA/2)F1, (A/Sn × DBA/2)F1, and (A/J × DBA/2)F1 mice] revealed that: a) The expressions of NAb and NK cell specificities associated with the YAC-1 tumor were directly related and could not be distinguished on the basis of inhibition and absorption studies, whereas the expressions of the specificities associated with a second NK cell-sensitive tumor, the SL2 lymphoma, were not directly related. b) Treatment of mice with the adjuvants proteose peptone and lipopolysaccharide or the interferon inducers polyinosinic-polycytidylic acid and 2-amino-5-bromo-6-methyl-4-pyrimidinol resulted in increases in NAb levels and NK cells, which suggested that certain aspects of the regulation of these activities may be similar or the same. c) High NK cell activity was codominantly inherited and high serum NAb levels were recessive, which argues against the theory that the NK cell receptor is a passively acquired NAb. d) NK cell activity declined with increasing age in contrast with NAb levels that remained constant throughout adult life. e) Bg/Bg mutants that exhibit an NK cell defect expressed normal levels of NAb. Despite the differences in their genetics, murine antitumor NAb and NK cells bear certain common features-in particular, their response to microbial products and interferon inducers and at least a portion of the antigen repertoire against which they are directed.

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