The Journal of Experimental Medicine
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© The Rockefeller University Press, 0022-1007/1998/5/1611/ $5.00
The Journal of Experimental Medicine, Volume 187, Number 10, May 18, 1998 1611-1621


Articles

Abortive Proliferation of Rare T Cells Induced by Direct or Indirect Antigen Presentation by Rare B Cells In Vivo

Sarah E. Townsend and Christopher C. Goodnow

From the Howard Hughes Medical Institute and Department of Microbiology and Immunology, Stanford University, Stanford, California 94305; and Medical Genome Center and Australian Cancer Research Foundation Genetics Laboratory, John Curtin School of Medical Research, Canberra ACT 2601, Australia

Antigen-specific B cells are implicated as antigen-presenting cells in memory and tolerance responses because they capture antigens efficiently and localize to T cell zones after antigen capture. It has not been possible, however, to visualize the effect of specific B cells on specific CD4+ helper T cells under physiological conditions. We demonstrate here that rare T cells are activated in vivo by minute quantities of antigen captured by antigen-specific B cells. Antigen-activated B cells are helped under these conditions, whereas antigen-tolerant B cells are killed. The T cells proliferate and then disappear regardless of whether the B cells are activated or tolerant. We show genetically that T cell activation, proliferation, and disappearance can be mediated either by transfer of antigen from antigen-specific B cells to endogenous antigen-presenting cells or by direct B–T cell interactions. These results identify a novel antigen presentation route, and demonstrate that B cell presentation of antigen has profound effects on T cell fate that could not be predicted from in vitro studies.

Key Words: peripheral tolerance • antigen-presenting cell • interactions • B cell • T cell


Address correspondence to Christopher C. Goodnow, The Medical Genome Center, John Curtin School of Medical Research, Mills Road, PO box 334, ACT 2601, Australia. Phone: 61-2-6249-3621; Fax: 61-2-6279-8512; E-mail: chris.goodnow{at}anu.edu.au

Abbreviations used: BCR, B cell receptor; HEL, hen egg lysozyme; sHEL, soluble HEL; CFSE, 5- (and 6-) carboxyfluorescein diacetate succinimidyl ester.


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