The Journal of Experimental Medicine
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© The Rockefeller University Press, 0022-1007/1997/8/673/ $5.00
The Journal of Experimental Medicine, Volume 186, Number 5, August 29, 1997 673-682

Article

Antigen-unspecific B Cells and Lymphoid Dendritic Cells Both Show Extensive Surface Expression of Processed Antigen–Major Histocompatibility Complex Class II Complexes after Soluble Protein Exposure In Vivo or In Vitro

Guangming Zhong, Caetano Reis e Sousa, and Ronald N. Germain

From the Lymphocyte Biology Section, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892-1892

Intravenous (i.v.) injection of high amounts of soluble proteins often results in the induction of antigen-specific tolerance or deviation to helper rather than inflammatory T cell immunity. It has been proposed that this outcome may be due to antigen presentation to T cells by a large cohort of poorly costimulatory or IL-12–deficient resting B cells lacking specific immunoglobulin receptors for the protein. However, previous studies using T cell activation in vitro to assess antigen display have failed to support this idea, showing evidence of specific peptide–major histocompatibility complex (MHC) class II ligand only on purified dendritic cells (DC) or antigen-specific B cells isolated from protein injected mice. Here we reexamine this question using a recently derived monoclonal antibody specific for the T cell receptor (TCR) ligand formed by the association of the 46-61 determinant of hen egg lysozyme (HEL) and the mouse MHC class II molecule I-Ak. In striking contrast to conclusions drawn from indirect T cell activation studies, this direct method of TCR ligand analysis shows that i.v. administration of HEL protein results in nearly all B cells in lymphoid tissues having substantial levels of HEL 46-61–Ak complexes on their surface. DC readily isolated from spleen also display this TCR ligand on their surface. Although the absolute number of displayed ligands is greater on such DC, the relative specific ligand expression compared to total MHC class II levels is similar or greater on B cells. These results demonstrate that in the absence of activating stimuli, both lymphoid DC and antigen-unspecific B cells present to a similar extent class II–associated peptides derived from soluble proteins in extracellular fluid. The numerical advantage of the TCR ligand–bearing B cells may permit them to interact first or more often with naive antigen-specific T cells, contributing to the induction of high-dose T cell tolerance or immune deviation.

Address correspondence to Dr. Ronald N. Germain, LBS/LI/NIAID/DIR, Building 10, Room 11N311, 10 Center Drive, MSC 1892, National Institutes of Health, Bethesda, MD 20892-1892. Phone: 301-496-1904; FAX: 301-496-0222; E-mail: Ronald_Germain{at}nih.gov. G. Zhong's present address is Department of Medical Microbiology, University of Manitoba, Winnipeg, Manitoba R3E OW3, Canada.

G. Zhong and C. Reis e Sousa are supported by Visiting Fellowships from the Fogarty International Center.

1 Abbreviations used in this paper: DC, dendritic cells; HEL, hen egg lysozyme; HRP, horseradish peroxidase; LOD, low density spleen; WT, wild-type.

G. Zhong and C. Reis e Sousa contributed equally to this work.


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