HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Data Supplement All Versions of this Article: jimmunol.0901391v1 183/6/3608    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Google Scholar Articles by Haddad, E. A. Articles by Takei, F. PubMed PubMed Citation Articles by Haddad, E. A. Articles by Takei, F.

An Accessory Role for B Cells in the IL-12-Induced Activation of Resting Mouse NK Cells¹

Evette A. Haddad^*, Laura K. Senger^* and Fumio Takei^2,*,

^* Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, British Columbia, Canada; and Department of Pathology and Laboratory Medicine, University of British Columbia Vancouver, British Columbia, Canada

IL-12 is a potent proinflammatory cytokine. The effects of IL-12 are thought to be mediated by IFN- production by NK, NKT, and T cells. In this study, we show that although IL-12 stimulates NK and NK1.1⁺ T cells in bulk mouse splenocytes, it does not significantly stimulate purified NK cells, indicating that other cells are required. IL-12 stimulates T cell-deficient spleen cells and those depleted of macrophages. Unexpectedly, the depletion of dendritic cells also has little effect on the stimulation of spleen cells with IL-12. In contrast, B cell depletion almost completely inhibits IL-12-induced IFN- production and B cell-deficient spleen cells are poorly stimulated with IL-12. Furthermore, purified NK cells are stimulated with IL-12 in the presence of purified B cells. Thus, B cells are necessary and also sufficient for the stimulation of purified NK cells with IL-12. Whereas spleen cells from IL-18-deficient mice are not stimulated with IL-12, NK cells purified from IL-18-deficient mice are stimulated with IL-12 in the presence of wild-type (WT) B cells, and WT NK cells are not stimulated with IL-12 in the presence of IL-18-deficient B cells. Cell contact between B and NK cells is also required for IL-12-induced IFN- production. Finally, B cell-deficient mice injected with IL-12 produce significantly less IFN- and IL-18 in the sera than WT mice do. Thus, stimulation of NK cells with IL-12 requires B cell cooperation in vitro as well as in vivo.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by grants from the Canadian Cancer Society.

² Address correspondence and reprint requests to Dr. Fumio Takei, Terry Fox Laboratory, British Columbia Cancer Research Centre, 675 West 10th Avenue, Vancouver, British Columbia, Canada V5Z 1L3. E-mail address: ftakei{at}bccrc.ca

³ Abbreviations used in this paper: DC, dendritic cell; KO, knockout; WT, wild type.

⁴ The online version of this article contains supplemental material.