The Journal of Experimental Medicine, Vol 134, 1266-1284,
Copyright © 1971 by The Rockefeller University Press
CELL-TO-CELL INTERACTION IN THE IMMUNE RESPONSE
:
VII. REQUIREMENT FOR DIFFERENTIATION OF THYMUS-DERIVED CELLS
J. F. A. P. Miller F.R.S.1,
J. Sprent M.B.1,
A. Basten M.B.1,
N. L. Warner Ph.D.1,
J. C. S. Breitner M.D.1,
G. Rowland Ph.D.1,
J. Hamilton Ph.D.1,
H. Silver B.Sc.1, and
W. J. Martin M.B.1
1 From the Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria 3050, Australia
Experiments were designed to test the possibility that thymus-derived (T) cells cooperate with nonthymus derived (B) cells in antibody responses by acting as passive carriers of antigen. Thoracic duct lymphocytes (TDL) from fowl 
G-tolerant mice were incubated in vitro with fowl anti-mouse lymphocyte globulin (FALG), which was shown not to be immunosuppressive in mice. On transfer into adult thymectomized, irradiated, and marrow protected (TxBM) hosts together with a control antigen, horse RBC, a response to horse RBC but not to fowl G was obtained. By contrast, TxBM recipients of nontolerant, FALG-coated TDL responded to both antigens and the antibody-forming cells were shown to be derived from the host, not from the injected TDL. These findings suggested that, under the conditions of the experiment, triggering of unprimed B cells in the spleens of TxBM hosts was not achieved with antigen-coated tolerant lymphocytes.
Another model utilized the ability of B cells to bind antibody-antigen complexes. Spleen cells from TxBM mice, incubated in vitro with anti-fowl G-fowl G·NIP, were injected with or without normal TDL (a source of T cells) into irradiated hosts. Only mice given both cell types could produce an anti-NIP antibody response. In a further experiment, spleen cells from HGG·NIP-primed mice were injected together with NIP-coated B cells (prepared as above) into irradiated hosts. A substantial anti-NIP antibody response occurred. If, however, the T cells in the spleens of HGG·NIP-primed mice were eliminated by treatment with anti-
serum and complement, the NIP response was abolished. It was concluded that antigen-coated B cells could not substitute for T cells either in the primary or secondary response.
Treatment of T cells from unprimed or primed mice with mitomycin C impaired their capacity to collaborate with B cells on transfer into irradiated hosts. Taken together these findings suggest that before collaboration can take place T cells must be activated by antigen to differentiate and in so doing may produce some factor essential for triggering of B cells.
Submitted on July 2, 1971
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