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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, 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.

History

Publication title

The Journal of Experimental Medicine

Volume

188

Issue

8

Pagination

1503-1510

ISSN

0022-1007

Department/School

Menzies Institute for Medical Research

Publisher

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

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