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Fibroblastic Reticular Cells Guide T Lymphocyte Entry into and Migration within the Splenic T Cell Zone¹

Marc Bajénoff^*,,, Nicolas Glaichenhaus and Ronald N. Germain^2,*

^* Lymphocyte Biology Section, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892; and Institut National de la Santé et de la Recherche Médicale and Centre National de la Recherche Scientifique, Université de Nice-Sophia Antipolis, Valbonne, France

Although a great deal is known about T cell entry into lymph nodes, much less is understood about how T lymphocytes access the splenic white pulp (WP). We show in this study that, as recently described for lymph nodes, fibroblastic reticular cells (FRCs) form a network in the T cell zone (periarteriolar lymphoid sheath, PALS) of the WP on which T lymphocytes migrate. This network connects the PALS to the marginal zone (MZ), which is the initial site of lymphocyte entry from the blood. T cells do not enter the WP at random locations but instead traffic to that site using the FRC-rich MZ bridging channels (MZBCs). These data reveal that FRCs form a substrate for T cells in the spleen, guiding these lymphocytes from their site of entry in the MZ into the PALS, within which they continue to move on the same network.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This research was supported in part by the Intramural Research Program of National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, by the Institut de la Santé et de la Recherche Médicale (INSERM), and by the Centre National de la Recherche Scientifique (CNRS).

² Address correspondence and reprint requests to Dr. Ronald N. Germain, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Building 10, Room 11N-311, 10 Center Drive, MSC 1892, Bethesda, MD 20892. E-mail address: rgermain{at}niaid.nih.gov

³ Abbreviations used in this paper: LN, lymph node; WP, white pulp; RP, red pulp; MZ, marginal zone; MMM, marginal metallophilic macrophage; PALS, periarteriolar lymphoid sheath; FRC, fibroblastic reticular cell; MZBC, marginal zone bridging channel; 2P, two photon.

⁴ The online version of this article contains supplemental material.