University Of Tasmania

File(s) not publicly available

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, A
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.


Publication title

The Journal of Experimental Medicine










Menzies Institute for Medical Research


Rockefeller Univ Press

Place of publication

1114 First Ave, 4Th Fl, New York, USA, Ny, 10021

Repository Status

  • Restricted

Socio-economic Objectives

Clinical health not elsewhere classified

Usage metrics