IMMUNOLOGICAL PROPERTIES OF BACTERIAL LIPOPOLYSACCHARIDE (LPS) .4. CELLULAR BASIS OF UNRESPONSIVENESS OF C3H-HEJ MOUSE SPLEEN-CELLS TO LPS-INDUCED MITOGENESIS

  • 1 January 1977
    • journal article
    • research article
    • Vol. 118  (1) , 274-281
Abstract
Lymphoid cells obtained from the C3H/HeJ mouse strain respond abnormally to [Escherichia coli] LPS in vitro. They are unable to make a mitogenic response to some LPS preparations and make only a low mitogenic response to other LPS preparations. 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 [bone marrow-derived] cells, T [thymus-derived] cells and macrophages from C3H/HeJ and C3H/St mice. Experiments utilizing an LPS preparation to which C3H/HeJ mice are totally unresponsive (negative LPS) revealed that spleen cells or partially purified T cells and/or macrophages obtained from C3H/St mice 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. The addition of spleen cells or partially purified T cells or macrophages from C3H/HeJ mice to spleen cells from C3H/St mice 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 C3H/HeJ are partially responsive (positive LPS), also failed to demonstrate reconstitutive or suppressive effects when C3H/HeJ and C3H/St mouse spleen cells were admixed. 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.