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Generation of splenic follicular structure and B cell movement in tumor necrosis factor-deficient mice
journal contribution
posted on 2023-05-17, 07:44 authored by Cook, MC, Heinrich KornerHeinrich Korner, Riminton, DS, Lemckert, FA, Hasbold, J, Amesbury, M, Hodgkin, PD, Cyster, JG, Sedgwick, JD, Basten, ASecondary 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.
History
Publication title
The Journal of Experimental MedicineVolume
188Issue
8Pagination
1503-1510ISSN
0022-1007Department/School
Menzies Institute for Medical ResearchPublisher
Rockefeller Univ PressPlace of publication
1114 First Ave, 4Th Fl, New York, USA, Ny, 10021Repository Status
- Restricted