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Blood, 15 July 2005, Vol. 106, No. 2, pp. 593-600.
Prepublished online as a Blood First Edition Paper on April 12, 2005; DOI 10.1182/blood-2004-12-4630.
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IMMUNOBIOLOGY
Regional induction of adhesion molecules and chemokine receptors explains disparate homing of human B cells to systemic and mucosal effector sites: dispersion from tonsils
Finn-Eirik Johansen,
Espen S. Baekkevold,
Hege S. Carlsen,
Inger Nina Farstad,
Dulce Soler, and
Per Brandtzaeg
From the Laboratory for Immunohistochemistry and Immunopathology (LIIPAT), Institute and Department of Pathology, University of Oslo, Rikshospitalet University Hospital, Oslo, Norway; and the Inflammation Department, Millennium Pharmaceuticals Inc, Cambridge, MA.
Ethical constraints restrict direct tracking of immune-cell migration throughout the human body in vivo. We, therefore, used deletion of the immunoglobulin M (IgM) heavy-chain constant-gene (Cµ) segment as a marker to provide a dispersal signature of an effector B-cell subset (IgD+IgM-CD38+) induced selectively in human tonsils. By DNA analysis, the Cµ deletion identified dissemination of such blasts and their plasma-cell progeny to peripheral blood, lymph nodes, and bone marrow, as well as to mucosae and glands of the upper airways. Also the endocervix was often positive, while the small intestine was mainly negative, as could be expected from the identified homing-molecule profile of the marker cells, with relatively low levels of integrin  4 7 and CC chemokine receptor 9 (CCR9). Of further importance for vaccine design, the circulating cells expressed abundantly CD62L (L-selectin) and CCR7, which provided a mechanism for integration of respiratory and systemic immunity. Most mucosal vaccines are at present administered perorally, and our results suggested that the nasal route is no alternative for vaccination against rotavirus or other small-intestinal infections in humans. However, immunization of nasopharynx-associated lymphoid tissue clearly appears preferable to target respiratory pathogens and may to some extent also protect against infections of the female genital tract. (Blood. 2005;106:593-600)
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