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Antigens in the form of immune complexes are retained on the membranes of follicular dendritic cells (FDC) for long periods of time. To examine how immune complexes reach germinal centers, where FDC are located, we injected mice with anti-2,4-dinitrophenyl (DNP) antibodies complexed to DNP-myoglobin-coated gold particles. The distribution of the particles in spleens or draining lymph nodes was then determined with the electron microscope. The vast majority of the particles were cell bound. Shortly after injection they were phagocytized by macrophages or fixed on lymphocytes. The latter were found even in the corona of lymph follicles but not in germinal centers. Already 30 min after injection, FDC in contact with the corona were faintly positive but were negative in the center. FDC precursor cells were occasionally observed but in too small a number to account for the transport of immune complexes to the germinal centers. Twenty-four hours after injection colloidal gold particles were found in phagolysosomes of macrophages or on cytoplasmic extensions of FDC in all parts of the germinal centers. Experiments performed on isolated FDC showed that they are not only able to take up free immune complexes but are also able to adsorb immune complexes from pulsed lymphocytes. These results strengthen the idea that lymphoid cells binding immune complexes by their Fc receptors may transport these complexes inside germinal centers.

KEYWORDS:Neuropeptide signals and specific neuropeptide receptors have been described in the thymus supporting the concept of a close dialogue between the neuroendocrine and the immune systems at the level of early T-cell differentiation. In this paper, we review recent data about neurohypophysial (NHP)-related peptides detected in the thymus from different species. We suggest that we are dealing in fact with other member(s) of the NHP hormone family, which seems to exert its activity locally through a novel model of cell-to-cell signaling, that of cryptocrine communication. This model involves exchange of signals between thymic epithelial cells and developing thymocytes. The NHP-related peptides have been shown to trigger thymocyte proliferation and could induce immune tolerance of this highly conserved neuroendocrine family.Oxytocin, vasopressin, thymic epithelium, neurohypophysial peptide receptors, self-recognition, cryptocrine signaling. INTRODUCTIONIn the last decade, a number of studies has been reported indicating that various neuropeptides could be found in the thymus or in thymic neoplasms. Thus, neurotensin (NT) (Sundler et al., 1978;Herbst et al., 1987), somatostatin (SS) (Sundler et al., 1978;Geppetti et al., 1987;Fuller and Verity, 1989;Gomariz et al., 1990), oxytocin (OT) (Geenen et al., 1986;Ervin et al., 1988; Argiolas et al., 1990a;Jevremovic et al., 1990), vasopressin (VP) (Markwick et al., 1986;Geenen et al., 1987;Giraud et al., 1990), neurophysins (NPs) (Geenen et al., 1986), tachykinins (TKs) (Geppetti et al., 1988;Weihe et al., 1989;Ericsson et al., 1990;Lorton et al., 1990;Piantelli et al., 1990), neuropeptide Y (NPY) (D'Andrea et al., 1989;Weihe et al., 1989;Ericsson et al., 1990), vasoactive intestinal peptide (VIP) (Felten et al., 1985;Gomariz et al., 1990;A1-Shawaf et al., 1991), calcitonin gene-related peptide (CGRP) (Geppetti et al., 1989;Weihe et al., 1989), opioid peptides (Von Gaudecker et al., 1986;Piantelli et al., 1990), corticotropin (ACTH) (Her.bst et al., 1987), cholecystokinin (CCK) (Herbst et al., 1987), and atrial *Corresponding author. natriuretic peptide (ANP) (Vollmar and Schulz, 1990) have been immunologically, biologically, biochemically, and/or molecularly evidenced. These neuropeptides were not systematically located in the thymic structures. However, some immunoreactive (ir-) neuropeptides were localized in nerve fibers: substance P (SP) (Geppetti et al., 1987(Geppetti et al., , 1988Weihe et al., 1989;Lorton et al., 1990), CGRP (Weihe et al., 1989), VIP (Felten et al., 1985;A1-Shawaf et al., 1991), NPY (D'Andrea et al., 1989;Weihe et al., 1989). On the other hand, it was suggested that ANP could be localized in thymocytes (Vollmar and Schulz, 1990). Furthermore, NT and SS immunoreactivities were found in sparse stromal cells (Sundler et al., 1978), whereas neurokinin A (NKA) (Ericsson et al., 1990), opioid peptides (Von Gaudecker et al., 1986;Piantelli et al., 1990), OT, VP, and NPs (Robert et al., 1991) were localized in thymic epithelial c...

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We have investigated which areas produce interleukin 6 (IL 6) in human tonsils. This growth factor is required for the terminal differentiation of B lymphocytes into plasmocytes. Using 35S-labeled IL 6 cDNA we demonstrated IL 6 gene expression over various areas of the tonsils, with consistent exception of the follicles, by in situ hybridization. It is, therefore, proposed that B cells are stimulated during their migration out of the follicles.