File(s) not publicly available
Generation of splenic follicular structure and B cell movement in tumor necrosis factor-deficient mice
journal contributionposted 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 Î± (LTÎ±). 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/LTÎ±(-/-) 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/LTÎ±(-/-) recipients. This result appeared to account for the defect in isotype switching observed in intact TNF/LTÎ±(-/-) mice because TNF/LTÎ±(-/-) 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 titleThe Journal of Experimental Medicine
Department/SchoolMenzies Institute for Medical Research
PublisherRockefeller Univ Press
Place of publication1114 First Ave, 4Th Fl, New York, USA, Ny, 10021