Generation of splenic follicular structure and B cell movement in tumor necrosis factor-deficient mice.
AuthorCook, MC; Körner, H; Riminton, DS; Lemckert, FA; Hasbold, J; Amesbury, M; Hodgkin, PD; Cyster, JG; Sedgwick, JD; Basten, A
Source TitleJournal of Experimental Medicine
PublisherRockefeller University Press
University of Melbourne Author/sHodgkin, Philip
AffiliationMedical Biology (W.E.H.I.)
Document TypeJournal Article
CitationsCook, M. C., Körner, H., Riminton, D. S., Lemckert, F. A., Hasbold, J., Amesbury, M., Hodgkin, P. D., Cyster, J. G., Sedgwick, J. D. & Basten, A. (1998). Generation of splenic follicular structure and B cell movement in tumor necrosis factor-deficient mice.. J Exp Med, 188 (8), pp.1503-1510. https://doi.org/10.1084/jem.188.8.1503.
Access StatusOpen Access
Open Access at PMChttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC2213402
Secondary lymphoid tissue organogenesis requires tumor necrosis factor (TNF) and lymphotoxin alpha (LTalpha). 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/LTalpha-/- 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/LTalpha-/- recipients. This result appeared to account for the defect in isotype switching observed in intact TNF/LTalpha-/- mice because TNF/LTalpha-/- 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.
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