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Studies of the Mechanism by Which B Cells Permit Mixed Lymphocyte Reactions between Immunocompetent Thymus Cells¹

From the Tumor Biology Unit, Department of Pathology, University of Florida College of Medicine, Gainesville, Florida 32610 and the C. V. Whitney Laboratory for Experimental Marine Biology and Medicine, St. Augustine, Florida 32084

Abstract

The mechanisms by which a critical ratio of peripheral lymphoid helper cells permit a proliferative MLR response between congenic immunocompetent thymus cell subpopulations was investigated. The helper cell was found to be contained in a subpopulation of B cells on the basis of sensitivity to anti-Ig and complement, resistance to anti-Thy-1.2, adherence to nylon columns, and ability to form EA and EAC rosettes with sheep erythrocytes. The maximal helper cell effect was obtained in those combinations in which helper was syngeneic for responder. Helper cells of F₁ hybrid origin or syngeneic to stimulator cells were less effective. Kinetic studies indicated that the first of the sequence of events is helper cell-stimulator cell interaction, followed by triggering of responder proliferation generating a subset of cytotoxic cells. Helper activity was trypsin sensitive, and present in solubilized preparation of peripheral cells. Helper activity of intact cells was nearly matched quantitatively by critical ratios of polyclonal IgG, IgG subclasses, and IgG fragment preparations, but little activity was supplied by IgA and IgM preparations. Kinetics studies of IgG helper activity indicate dose-response effects and sequence of interaction similar to those found for whole B cells. A hypothesis is offered to explain how the B-helper or its product may permit an otherwise nonreactive MLR between immunocompetent thymus cells.

Footnotes

¹ This work was supported in part by National Institute of Health Grants AI-00401, CA-15334, HD-00384, CA-09126 and gifts to the Mary and Ryan Whisenant Cancer Research Fund. This is publication No. 109 from the Tumor Biology Unit, Department of Pathology, University of Florida College of Medicine, Gainesville, Florida 32610.

² Recipient of National Institute of Allergy and Infectious Diseases Research Fellowship AI-01555.

³ Present address: Hematology-Oncology Division, Children's Hospital Medical Center, Cincinnati, Ohio 45229.

⁴ Address reprint requests to the Tumor Biology Unit, Department of Pathology, Box J-275 JHMHC, University of Florida College of Medicine, Gainesville, Florida, 32610.