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Generation of splenic follicular structure and B cell movement in tumor necrosis factor-deficient mice


Cook, MC and Korner, H and Riminton, DS and Lemckert, FA and Hasbold, J and Amesbury, M and Hodgkin, PD and Cyster, JG and Sedgwick, JD and Basten, A, Generation of splenic follicular structure and B cell movement in tumor necrosis factor-deficient mice, The Journal of Experimental Medicine, 188, (8) pp. 1503-1510 . ISSN 0022-1007 (1998) [Refereed Article]

DOI: doi:10.1084/jem.188.8.1503


Secondary lymphoid tissue organogenesis requires tumor necrosis factor (TNF) and lymphotoxin α (LTα). 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/LTα(-/-) 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/LTα(-/-) recipients. This result appeared to account for the defect in isotype switching observed in intact TNF/LTα(-/-) mice because TNF/LTα(-/-) 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.

Item Details

Item Type:Refereed Article
Research Division:Biomedical and Clinical Sciences
Research Group:Immunology
Research Field:Immunology not elsewhere classified
Objective Division:Health
Objective Group:Clinical health
Objective Field:Clinical health not elsewhere classified
UTAS Author:Korner, H (Professor Heinrich Korner)
ID Code:72443
Year Published:1998
Web of Science® Times Cited:43
Deposited By:Research Division
Deposited On:2011-08-26
Last Modified:2011-08-29

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