Activation of mouse lymphocytes by anti-immunoglobulin. II. A thymus-independent response by a mature subset of B lymphocytes.

Abstract

Mouse spleen cells can be stimulated to proliferate in vitro by purified anti-.mu. or anti-.gamma.,.kappa. antibodies. These responses can be obtained in cell populations bearing membrane immunoglobulin (Ig), purified by the fluorescence activated cell sorter (FACS), but they are not observed in FACS-purified Ig- cell populations. Treatment of spleen cell populations with anti-Thy 1.2 and complement does not impair the response, nor does addition of nylon wool-purified T [thymus derived] lymphocytes enhance it. Thus B [bone marrow derived] lymphocytes respond to anti-Ig and their response does not require T cells. Cells from athymic nude (nu/nu) mice respond slightly less well to anti-.mu. than do cells from heterozygous littermate (nu/+) controls; nu/nu cells are almost unresponsive to anti-.gamma.,.kappa. and addition of nylon wool-purified T cells from nu/+ controls does not restore the response. Thus T lymphocytes or the thymus may control the appearance of cells responsive to anti-.gamma.,.kappa.. Responsiveness of normal mice to anti-.mu. does not appear until 4 wk of age and does not reach maximum levels until 8 wk of age. Acquisition of full responsiveness to anti-.gamma.,.kappa. is even more delayed. This, together with the failure of mice with the CBA/N B-cell defect to respond to anti-Ig, suggests that cells stimulated to proliferate by anti-Ig are a mature subset of B cells. Depletion of adherent cells by Sephadex G-10 treatment or by treatment with carbonyl Fe and exposure to a magnetic field does not diminish anti-.mu. or anti-.gamma.,.kappa. responses, suggesting that the responsiveness does not require the presence of macrophages. Activation of B-cell proliferation by anti-Ig appears to be a T-cell independent, macrophage-independent process in which membrane Ig plays a direct role in signal generation.