Polarized expression of cytokines in cell conjugates of helper T cells and splenic B cells.
We describe the intracellular localization, by double immunofluorescence microscopy, of four cytokines that were produced during the prolonged interaction of cloned helper T cells with resting splenic B cells. When two rabbit immunoglobulin-specific helper-T-cell clones were mixed, either separately or together, with splenic B cells in the presence of the antigen rabbit anti-mouse immunoglobulin antibodies, stable T-cell-B-cell conjugates were seen up to 29 hr later. Microscopic observations of these cells revealed that interferon gamma and interleukin 2, inside one of the T-cell clones, and interleukins 4 and 5, inside the other T-cell clone, were concentrated very close to the T-cell-B-cell contact area. The cytokines were not seen in the T cells prior to their interaction with the B cells and their production was strictly antigen-specific. These studies show, at the single-cell level, that helper-T-cell clones can remain bound to splenic B cells long enough for the T cells to produce cytokines, which are synthesized near the bound B cells. We propose that the polarized synthesis of the cytokines may result in their directed secretion toward the bound B cells. By locally secreting the cytokines, which are not antigen-specific, at the contacting T-cell-B-cell membranes, where T- and B-cell surface receptors are engaged and clustered, the helper T cells can induce selective and specific B-cell responses.
Kupfer
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A
Department of Pediatrics, National Jewish Center for Immunology and Respiratory Medicine, Denver, CO 80206.
Mosmann
T R
TR
Kupfer
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H
D000818:Animals; D000911:Antibodies, Monoclonal; D001402:B-Lymphocytes / Q000166:cytology* / Q000276:immunology*; D002450:Cell Communication; D002454:Cell Differentiation; D016207:Cytokines / Q000032:analysis / Q000096:biosynthesis*; D005455:Fluorescent Antibody Technique; D007371:Interferon-gamma / Q000032:analysis; D007376:Interleukin-2 / Q000032:analysis; D015847:Interleukin-4 / Q000032:analysis; D015848:Interleukin-5 / Q000032:analysis; D007378:Interleukins / Q000032:analysis / Q000096:biosynthesis*; D051379:Mice; D008815:Mice, Inbred Strains; D013154:Spleen / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology / Q000276:immunology*
D000911:Antibodies, Monoclonal; D016207:Cytokines; D007376:Interleukin-2; D015848:Interleukin-5; D007378:Interleukins; D015847:Interleukin-4; D007371:Interferon-gamma