Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents

This Article Full Text Full Text (PDF, 21426K) PPT slides of all figures Alert me when this article is cited Citation Map Services Email this article Similar articles in this journal Similar articles in PubMed Alert me to new content in the JEM Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Cook, M. C. Articles by Basten, A. Search for Related Content PubMed PubMed Citation Articles by Cook, M. C. Articles by Basten, A. Social Bookmarking                            What's this?

Articles

Matthew C. Cook^*, Heinrich Körner^*, D. Sean Riminton^*, Frances A. Lemckert^*, Jhagvaral Hasbold^*, Michelle Amesbury^*, Philip D. Hodgkin, Jason G. Cyster, Jonathon D. Sedgwick^*, and Antony Basten^*

From the ^* Centenary Institute of Cancer Medicine and Cell Biology, Sydney, NSW, Australia 2050; the Medical Foundation of the University of Sydney, Sydney, NSW, Australia 2050; and the Department of Microbiology and Immunology, University of California at San Francisco, San Francisco, California 94143

Secondary lymphoid tissue organogenesis requires tumor necrosis factor (TNF) and lymphotoxin (LT). The role of TNF in B cell positioning and formation of follicular structure was studied by comparing the location of newly produced naive recirculating and antigen-stimulated B cells in TNF^–/– and TNF/LT^–/– mice. By creating radiation bone marrow chimeras from wild-type and TNF^–/– mice, formation of normal splenic B cell follicles was shown to depend on TNF production by radiation-sensitive cells of hemopoietic origin. Reciprocal adoptive transfers of mature B cells between wild-type and knockout mice indicated that normal follicular tropism of recirculating naive B cells occurs independently of TNF derived from the recipient spleen. Moreover, soluble TNF receptor–IgG fusion protein administered in vivo failed to prevent B cell localization to the follicle or the germinal center reaction. Normal T zone tropism was observed when antigen-stimulated B cells were transferred into TNF^–/– recipients, but not into TNF/LT^–/– recipients. This result appeared to account for the defect in isotype switching observed in intact TNF/LT^–/– mice because TNF/LT^–/– B cells, when stimulated in vitro, switched isotypes normally. Thus, TNF is necessary for creating the permissive environment for B cell movement and function, but is not itself responsible for these processes.

Key Words: tumor necrosis factor • lymphotoxin • B cell movement • germinal center • follicular structure

M.C. Cook's present address is Department of Immunology, University of Birmingham, Medical School, Edgbaston, Birmingham, B15 2TT, UK. H. Körner's present address is Institute for Microbiology, Hygiene and Immunology, Wasserturmstrasse 3, D-91054 Erlangen, Germany.

M.C. Cook and H. Körner contributed equally to this study.

Abbreviations used: BLR1, Burkitt lymphoma receptor 1; CFSE, 5-(and -6-)-carboxyfluorescein diacetate succinimidyl ester; FDC, follicular dendritic cell; GC, germinal center; HEL, hen egg lysozyme; LT, lymphotoxin; PALS, periarteriolar lymphoid sheath; PNA, peanut agglutinin; Tg, transgenic; TNFR-Ig, TNFR-1–IgG fusion protein; WT, wild-type.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

Home | Help | Feedback | Subscriptions | Archive | Search

TABLE OF CONTENTS