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The Journal of Immunology, 1977, 118: 274-281.
Copyright © 1977 by The American Association of Immunologists, Inc.

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Immunologic Properties of Bacterial Lipopolysaccharide (LPS)

IV. Cellular Basis of the Unresponsiveness of C3H/HeJ Mouse Spleen Cells to LPS-Induced Mitogenesis1

Barry J. Skidmore2, Jacques M. Chiller3 and William O. Weigle4

From Scripps Clinic and Research Foundation, Department of Immunopathology, La Jolla, California 92037

Abstract

Lymphoid cells obtained from the C3H/HeJ mouse strain respond abnormally to LPS in vitro, as shown by the fact that they are unable to make a mitogenic response to some LPS preparations and make only a low mitogenic response to other LPS preparations. In contrast, cells from a closely related C3H substrain, the C3H/St, are highly responsive to both types of LPS preparations. Experiments were carried out to determine the cellular basis of these genetically determined LPS response differences. This question was approached by studying the mitogenic response to LPS in cultures containing mixtures of various combinations of B cells, T cells, and macrophages from C3H/HeJ and C3H/St mice. Experiments utilizing an LPS preparation to which the C3H/HeJ is totally unresponsive (negative LPS) revealed, first, that either spleen cells, or partially purified T cells and/or macrophages obtained from C3H/St, could not restore the ability of C3H/HeJ spleen cells to respond to LPS, indicating that the C3H/HeJ is not deficient in an LPS-specific helper cell population which may be required for mitogenesis. Secondly, the addition of either spleen cells or partially purified T cells or macrophages from the C3H/HeJ to spleen cells from the C3H/St did not inhibit the mitogenic response to LPS, suggesting that the presence of suppressor cell activity is also not involved. Experiments analogous to those described, except utilizing another LPS preparation to which the C3H/HeJ is partially responsive (positive LPS), also failed to demonstrate reconstitutive or suppressive effects when C3H/HeJ and C3H/St spleen cells were admixed.

The results obtained indicate that the defect in the C3H/HeJ mouse strain that limits its responsiveness to positive LPS and which renders it totally unresponsive to negative LPS appears to be an intrinsic defect in the capacity of B cells to react to the mitogenic stimulus of LPS.

Footnotes

1 This is Publication No. 1142 from the Division of Immunology, Scripps Clinic and Research Foundation, La Jolla, California. This work was supported by United States Public Health Service Grant AI-07007, Atomic Energy Administration Contract E (04-3)-410 and American Cancer Society Grant IM-42E.

2 Supported by United States Public Health Service Training Grant AI-00453. Present address. Department of Cellular and Developmental Immunology, Scripps Clinic and Research Foundation, La Jolla, California 92037.

3 Supported by a Dernham Fellowship (No. D-202) of the California Division of the American Cancer Society. Present address: Department of Allergy and Clinical Immunology, National Jewish Hospital and Research Center, 3800 East Colfax Avenue, Denver, Colorado 80206.

4 Recipient of United States Public Health Service Research Career Development Award No. 5-K6-GM-6936. To whom reprint requests should be addressed.







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