Regulation of T Cell Mitogen Activity of Anti-Lymphocyte Serum by a B-Helper Cell

Abstract

Rabbit anti-mouse brain antiserum (RaMB) was found to be mitogenic for mouse lymphocytes by using a ³H-thymidine incorporation assay. The mitogenic activity was maximal at 48 hr incubation and was absorbable with brain and T lymphocytes. Specificity was directed toward a Thy-1 like molecule without Thy-1 allotypic restrictions. Mixed populations of lymphocytes from spleen and lymph node were highly responsive to low concentrations of RaMB at which purified subpopulations of T or B lymphocytes were unresponsive. T cell responses could be reconstituted by addition of B-enriched cell subpopulations. Macrophages had no helper effect; rather they inhibited the response even at very low numbers of cells. Proliferative responses in mixed populations involved both T and B cell subpopulations in which the T cell component accounted for 80 to 90%, and the B cell subpopulation about 10 to 20% of net thymidine incorporation. B cell proliferation was not required for the regulatory effect. No B cell helper activity was detectable if F(ab′)₂ fragments prepared from RaMB-Ig were used as mitogen. The data suggest that T cell activation by anti-T cell serum first involved ligand-antibody interaction. This is a necessary but insufficient cell surface event to trigger proliferation. A second interaction appears to be required to initiate proliferation. The data suggest that the Fc region of the bound antibody molecule supplies this impetus by engaging the Fc receptor of the B-helper cell.